The objective was to evaluate steer performance, meat nutritional value, land-use, food–feed competition and both economic and environmental sustainability within temperate pasture-based suckler weanling-to-beef systems with or without (forage-only) concentrates. Post-weaning, 8-month-old, late-maturing breed steers (333 kg) were assigned to one of three systems: (1) grass silage + 1.2 kg concentrate DM (148 days), followed by pasture (123 days) and finished on ad libitum concentrates (120 days) – slaughter age, 21 months (GRAIN); (2) as per (1) but pasture (196 days) and finished on grass silage ad libitum + 3.5 kg concentrate DM (124 days) – slaughter age, 24 months (SIL + GRAIN); and (3) grass silage-only (148 days), pasture (196 days), silage-only (140 days) and finished on pasture (97 days) – slaughter age, 28 months (FORAGE). The mean target carcass weight was 390 kg for each system. Data generated were used to parameterize a farm-level beef systems model. Concentrate DM intake was 1187, 606 and 0 kg/head for GRAIN, SIL + GRAIN and FORAGE, respectively. The forage-only (FORAGE) system offers several advantages, including improved farm profitability, enhanced meat fatty acid profile and only utilized inedible human feed. Consequently, associated greenhouse gas (GHG) emissions per net human edible food produced were more favourable for FORAGE. However, compared to GRAIN, the FORAGE system had an older age at slaughter and associated increased pasture land-use and GHG emissions per animal, meat weight gain and essential amino acids gain. There are therefore inevitable trade-offs, as one beef system does not improve all sustainability and GHG emission metrics.

Background: Antibiotics alone are often insufficient to treat recurrent C. difficile infection (rCDI) because they have no activity against C. difficile spores that germinate within a disrupted microbiome. SER-109, an investigational, oral, microbiome therapeutic comprised of purified Firmicutes spores, was designed to reduce rCDI through microbiome repair. We report an integrated efficacy analysis through week 24 for SER-109 from phase 3 studies, ECOSPOR III and ECOSPOR IV. Methods: ECOSPOR III was a randomized, placebo-controlled phase 3 trial conducted at 56 US or Canadian sites that included 182 participants with ≥2 CDI recurrences, confirmed via toxin EIA testing. Participants were stratified by age (<65 years or ≥65 years) and antibiotic regimen (vancomycin, fidaxomicin) and were randomized 1:1 to placebo or SER-109 groups. ECOSPOR IV was an open-label, single-arm study conducted at 72 US or Canadian sites including 263 participants with rCDI enrolled in 2 cohorts: (1) rollover participants from ECOSPOR III who experienced on-study recurrence diagnosed by toxin EIA (n = 29) and (2) participants with ≥1 CDI recurrence (diagnosed by PCR or toxin EIA), inclusive of the current episode (n = 234). In both studies, the investigational product was administered orally as 4 capsules over 3 consecutive days following symptom resolution after standard-of-care antibiotics. The primary efficacy end point was rCDI (recurrent toxin-positive diarrhea requiring treatment) through week 8. Other end points included CDI recurrence rates and safety through 24 weeks. Results: These 349 participants received at least 1 dose of SER-109 in ECOSPOR III or ECOSPOR IV (mean age 64.2; 68.8% female). Overall, 77 participants (22.1%) enrolled with their first CDI recurrence. Four participants received blinded SER-109 in ECOSPOR III followed by a second dose of open-label SER-109 in ECOSPOR IV. Overall, the proportion of participants who received any dose of SER-109 with rCDI at week 8 was 9.5% (33 of 349; 95% CI, 6.6 %–13.0%), and the CDI recurrence rate remained low through 24 weeks (15.2%, 53 of 349; 95% CI, 11.6%–19.4%), corresponding to sustained clinical response rates of 90.5% (95% CI, 87.0%–93.4%) and 84.8% (95% CI, 80.6%–88.4%), respectively (Fig. 1). Most rollover participants (25 of 29, 86.2%) were from the placebo arm; 13.8% had rCDI by week 8. Conclusions: In this integrated analysis, the rates of rCDI were low and durable in participants who received the investigational microbiome therapeutic SER-109, with sustained clinical response rates of 90.5% and 84.8% at weeks 8 and 24, respectively. These data further support the potential benefit of microbiome repair with SER-109 following antibiotics for rCDI to prevent recurrence in high-risk patients.

Financial support: This study was funded by Seres Therapeutics.

Disclosure: None

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

Background: Despite guidelines recommending shorter durations of therapy and empiric coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) only for patients with certain risk factors, optimizing therapy for community-acquired pneumonia (CAP) remains a challenge for antimicrobial stewardship (AMS) teams. We investigated the impact of a multimodal AMS initiative on the rate of guideline-discordant empiric antibiotic selection and total duration of therapy for CAP. Methods: A quality improvement initiative was implemented at 9 community hospitals in 2022 to optimize CAP therapy. Education was provided to pharmacists and providers. Alerts were implemented within the electronic medical record to prompt the AMS team to review fluoroquinolones, antipseudomonal β-lactams, and anti-MRSA agents ordered for CAP. Clinical pharmacists reviewed antibiotic orders for CAP at hospital discharge and encouraged providers to prescribe a total antibiotic duration of 5–7 days. For the preintervention period (July– September 2021) and the postintervention period (July to September 2022), a random sample of 320 patients with an antibiotic order for CAP were evaluated retrospectively via chart review. Patients treated for an indication other than CAP were excluded. The primary outcome was the proportion of patients with a total duration of therapy >7 days. Secondary outcomes included average duration of therapy, rate of guideline-discordant empiric therapy, and type of guideline discordance. Results: In total, 317 patients were included. The proportion of patients with a total duration of therapy >7 days decreased from 29% to 14% (P < .01). Average duration of therapy and guideline-discordant empiric therapy also decreased significantly (Table 1). Conclusions: This multifaceted AMS initiative was associated with decreased guideline-discordant empiric therapy and decreased total duration of therapy for CAP.

Disclosures: None

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

HIV and severe wasting are associated with post-discharge mortality and hospital readmission among children with complicated severe acute malnutrition (SAM); however, the reasons remain unclear. We assessed body composition at hospital discharge, stratified by HIV and oedema status, in a cohort of children with complicated SAM in three hospitals in Zambia and Zimbabwe. We measured skinfold thicknesses and bioelectrical impedance analysis (BIA) to investigate whether fat and lean mass were independent predictors of time to death or readmission. Cox proportional hazards models were used to estimate the association between death/readmission and discharge body composition. Mixed effects models were fitted to compare longitudinal changes in body composition over 1 year. At discharge, 284 and 546 children had complete BIA and skinfold measurements, respectively. Low discharge lean and peripheral fat mass were independently associated with death/hospital readmission. Each unit Z-score increase in impedance index and triceps skinfolds was associated with 48 % (adjusted hazard ratio 0·52, 95 % CI (0·30, 0·90)) and 17 % (adjusted hazard ratio 0·83, 95 % CI (0·71, 0·96)) lower hazard of death/readmission, respectively. HIV-positive v. HIV-negative children had lower gains in sum of skinfolds (mean difference −1·49, 95 % CI (−2·01, −0·97)) and impedance index Z-scores (–0·13, 95 % CI (−0·24, −0·01)) over 52 weeks. Children with non-oedematous v. oedematous SAM had lower mean changes in the sum of skinfolds (–1·47, 95 % CI (−1·97, −0·97)) and impedance index Z-scores (–0·23, 95 % CI (−0·36, −0·09)). Risk stratification to identify children at risk for mortality or readmission, and interventions to increase lean and peripheral fat mass, should be considered in the post-discharge care of these children.

Suicide in later life is a pressing public health concern, which has likely been exacerbated by the COVID-19 pandemic. Many older adults who need mental health treatment do not have access to necessary services and training for mental health providers to support older adults experiencing suicidality is limited. One solution is developing interventions based in a public health approach to suicide prevention, whereby natural helpers who provide community services are mobilised to respond to older persons-at-risk. Home-delivered meal (HDM) services, for example, are one effective means to reach older adults who are isolated due to being homebound and may be instrumental in preventing suicide. This study examined the experiences of 20 HDM volunteers who received Applied Suicide Intervention Skills Training (ASIST), an evidence-based suicide intervention programme. Phenomenological analysis yielded findings centred on three areas demonstrating the impact of the ASIST training on HDM volunteers: putting asist skills into practice; response to ASIST skills; and role transformation. Implications for integrating suicide prevention efforts with HDM services and directions for future research are discussed.

Among bilinguals, language-related variables such as first and second language proficiency and balance may be related to important cognitive and academic outcomes, but approaches to characterizing these variables are inconsistent, particularly among at-risk samples of children. The current study employed comprehensive language assessment of English and Spanish language skills and contrasted various approaches to the characterization of language among at-risk ELs in middle school (N = 161). Specifically, we contrasted variable-centered and person-centered approaches, and convergence between objective and self-report measures. Findings support a two-factor structure of English and Spanish language skills in this population, three profiles of students (balanced, moderately unbalanced-higher Spanish, and very unbalanced-higher English), convergence between variable-centered and person-centered approaches, and mixed support for subjective indices of usage. Results provide a foundation from which to examine the roles of L1 and L2 proficiency as well as balance in important cognitive and academic outcomes in this at-risk and understudied population.

Hepatitis A virus (HAV) infection is a notifiable disease in Ireland, with national coverage of clinical and laboratory surveillance. In December 2020, a cluster of 11 HAV cases among the Irish Traveller community was detected. The outbreak investigation identified 61 total HAV cases from September 2020 to November 2021. Sequenced isolates were sub-genotype IA with identical genome sequence. Case-patients were predominantly aged under 18 (77%), hospitalised (46%) and lived on communal residential sites. Mass onsite HAV vaccination was employed following failure of initial ring vaccination to contain the outbreak. This is the largest outbreak of HAV described in Ireland, involving spillover to the UK and Netherlands. We recommend mass HAV vaccination and tailored communication for outbreak control in migratory subpopulations.