Background: Longer courses of antibiotics can be associated with antimicrobial resistance and adverse effects. Randomized clinical trials support treating gram-negative bloodstream infections (GN-BSI) for a shorter duration with a consensus that a seven-day course of antibiotics is appropriate for uncomplicated GN-BSI. Prior to the implementation of a GN-BSI treatment guideline at our institution, we aimed to evaluate the characteristics of patients with GN-BSI and the duration of antibiotic therapy (DOT). Method: We retrospectively reviewed adult inpatients who had a blood culture with at least 1 gram-negative organism within 6 months (November 2022 to April 2023). Patients were excluded if they had a concomitant gram-positive bloodstream infection or if they were transitioned to comfort-focused care within 48 hours of their first positive blood culture. Complicated GN-BSI was defined as exhibiting any of the following: involvement of bone, joint, endovascular system, or foreign body, an inability to achieve source control, immunocompromised status, or failure to demonstrate clinical improvement or culture clearance within 72 hours. The primary outcome of this study was the mean DOT in patients with GN-BSI. Result: 100 patients met the inclusion criteria. Escherichia coli, identified in 54 cases, emerged as the most frequent organism. Urine (41) was the predominant source of bacteremia. Cefepime (48) was the most common empiric agent used. Of the 91 patients with available ceftriaxone susceptibility results, 84% had a susceptible organism. Amongst the 51 patients classified as having a complicated GN-BSI, the leading reason was immunosuppression. Table 1 presents a comparative analysis of complicated vs. uncomplicated GN-BSI. The average DOT for complicated GN-BSI was longer than the uncomplicated infections (20 vs. 11 days, P < 0 .005). Additionally, fewer patients transitioned to oral therapy in the complicated group (33% vs. 67%, P < 0 .005). Conclusion: At our institution, patients with uncomplicated GN-BSI have a shorter DOT and are more likely to transition to oral therapy than those with complicated GN-BSI. However, the mean DOT for uncomplicated infections remained longer than seven days and a large number of uncomplicated GN-BSI patients did not transition to oral therapy, indicating room for improvement in local practice through antimicrobial stewardship initiatives.

OBJECTIVES/GOALS: Adoption of the Observational Medical Outcomes Partnership (OMOP) common data model promises to transform large-scale observational health research. However, there are diverse challenges for operationalizing OMOP in terms of interoperability and technical skills among coordinating centers throughout the US. METHODS/STUDY POPULATION: A team from the Critical Path Institute (C-Path) collaborated with the informatics team members at Johns Hopkins to provide technical support to participating sites as part of the Extract, Transform, and Load (ETL) process linking existing concepts to OMOP concepts. Health systems met regularly via teleconference to review challenges and progress in ETL process. Sites were responsible for performing the local ETL process with assistance and securely provisioning de-identified data as part of the CURE ID program. RESULTS/ANTICIPATED RESULTS: More than twenty health systems participated in the CURE ID effort.Laboratory measures, basic demographics, disease diagnoses and problem list were more easily mapped to OMOP concepts by CURE ID partner institutions. Outcomes, social determinants of health, medical devices, and specific treatments were less easily characterized as part of the project. Concepts within the medical record presented very different technical challenges in terms of representation. There is a lack of standardization in OMOP implementation even among centers using the same electronic medical health record. Readiness to adopt OMOP varied across the institutions who participated. Health systems achieved variable level of coverage using OMOP medical concepts as part of the initiative. DISCUSSION/SIGNIFICANCE: Adoption of OMOP involves local stakeholder knowledge and implementation. Variable complexity of health concepts contributed to variable coverage. Documentation and support require extensive time and effort. Open-source software can be technically challenging. Interoperability of secure data systems presents unique problems.

Background: Clostridioides difficile infection (CDI) often recurs in patients aged ≥65 years and those with comorbidities. Clinical trials often exclude patients with history of immunosuppression, malignancy, renal insufficiency, or other comorbidities. In a phase 3 trial (ECOSPOR III), SER-109 was superior to placebo in reducing recurrent CDI (rCDI) risk at week 8 and was well tolerated. We report integrated safety data for SER-109 in a broad patient population through week 24 from phase 3 studies: ECOSPOR III and ECOSPOR IV. Methods: ECOSPOR III was a double-blind, placebo-controlled trial conducted in participants with ≥2 CDI recurrences randomized 1:1 to placebo or SER-109. ECOSPOR IV was an open-label, single-arm study conducted in 263 patients with rCDI enrolled in 2 cohorts: (1) rollover participants from ECOSPOR III with on-study recurrence and (2) participants with ≥1 CDI recurrence, inclusive of the current episode. In both studies, the investigational product was administered as 4 oral capsules over 3 days. Treatment-emergent adverse events (TEAEs) were collected through week 8; serious TEAEs and TEAEs of special interest (ie, bacteremia, abscess, meningitis) were collected through week 24. Results: In total, 349 participants received SER-109 in ECOSPOR III and/or ECOSPOR IV (mean age 64.2; 68.8% female). Chronic diseases included cardiac disease (31.2%), immunocompromised or immunosuppressed (21.2%), diabetes (18.9% ), and renal impairment or failure (13.2%). Overall, 221 (63.3%) of 349 participants who received SER-109 experienced TEAEs through week 24. Most were mild to moderate and gastrointestinal. The most common (>5% of participants) treatment related TEAEs were flatulence, abdominal pain and distension, decreased appetite, constipation, nausea, fatigue, and diarrhea. No participants experienced a treatment-related TEAE leading to study withdrawal. Invasive infections were observed in 28 participants (8%); those with identified pathogens were unrelated to SER-109 species, and all were deemed unrelated to treatment by the investigators. There were 11 deaths (3.2%) and 48 participants (13.8%) with serious TEAEs, none of which were deemed treatment related. There were no clinically important differences in the safety profile across subgroups of sex, race, prior antibiotic regimen, or number of CDI recurrences. No safety signals were observed in participants with renal impairment or failure, diabetes, cardiac disease, or immunocompromised or immunosuppressed individuals. Conclusions: In this integrated analysis of phase 3 trials, SER-109, an investigational microbiome therapeutic, was well tolerated in this vulnerable patient population with prevalent comorbidities. No infections, nor those with identified pathogens, were attributed to SER-109 or product species. This safety profile might be expected because this purified product is composed of spore-forming Firmicutes normally abundant in the healthy microbiome.

Financial support: This study was funded by Seres Therapeutics.

Disclosures: None

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (−1·56 mmHg, 95 % CI −2·65, −0·48) and cMAP (−1·62 mmHg, 95 % CI −2·82, −0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (−0·93 %, 95 % CI −1·77, −0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.

Colleges and universities around the world engaged diverse strategies during the COVID-19 pandemic. Baylor University, a community of ˜22,700 individuals, was 1 of the institutions which resumed and sustained operations. The key strategy was establishment of multidisciplinary teams to develop mitigation strategies and priority areas for action. This population-based team approach along with implementation of a “Swiss Cheese” risk mitigation model allowed small clusters to be rapidly addressed through testing, surveillance, tracing, isolation, and quarantine. These efforts were supported by health protocols including face coverings, social distancing, and compliance monitoring. As a result, activities were sustained from August 1 to December 8, 2020. There were 62,970 COVID-19 tests conducted with 1435 people testing positive for a positivity rate of 2.28%. A total of 1670 COVID-19 cases were identified with 235 self-reports. The mean number of tests per week was 3500 with approximately 80 of these positive (11/d). More than 60 student tracers were trained with over 120 personnel available to contact trace, at a ratio of 1 per 400 university members. The successes and lessons learned provide a framework and pathway for similar institutions to mitigate the ongoing impacts of COVID-19 and sustain operations during a global pandemic.

This article examines the relationship between language shift and identity among diaspora Sindhis in India and Southeast Asia. It focuses on questions concerning how members of this community reproduce identity through language shift. The first part of the article describes identity and language shift among diaspora Sindhis in post-partition India. It argues that language shift facilitates the reproduction of core cultural modalities among diaspora Sindhis. The second part describes the history of diaspora Sindhis in Southeast Asia and analyses language shift. It contends that language shift enables diaspora Sindhis to suspend a connection between mother-tongue proficiency and identity. The article concludes by discussing how the diaspora Sindhi experience retunes the interval that conventionally connects language shift to cultural change.

Archaeological fieldwork preceding housing development revealed a Mesolithic site in a primary context. A central hearth was evident from a cluster of calcined flint and bone, the latter producing a modelled date for the start of occupation at 8220–7840 cal bc and ending at 7960–7530 cal bc (95% probability). The principal activity was the knapping of bladelets, the blanks for microlith production. Impact-damaged microliths indicated the re-tooling of hunting weaponry, while microwear analysis of other tools demonstrated hide working and butchery activity at the site. The lithics can be classified as a Honey Hill assemblage type on the basis of distinctive leaf-shaped microlithic points with inverse basal retouch.

Such assemblages have a known concentration in central England and are thought to be temporally intermediate between the conventional British Early and Late Mesolithic periods. The lithic assemblage is compared to other Honey Hill type and related Horsham type assemblages from south-eastern England. Both assemblage types are termed Middle Mesolithic and may be seen as part of wider developments in the late Preboreal and Boreal periods of north-west Europe. Rapid climatic warming at this time saw the northward expansion of deciduous woodland into north-west Europe. Emerging new ecosystems presented changes in resource patterns and the Middle Mesolithic lithic typo-technological developments reflect novel foraging strategies as adaptations to the new opportunities of Boreal forest conditions. While Honey Hill-type assemblages are seen as part of such wider processes their distinctive typological signature attests to autochthonous, regional developments of human groups infilling the landscape. Such cultural insularity may reflect changing social boundaries with reduction in mobility range and physical isolation caused by rising sea level and the creation of the British archipelago.