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

Clinical trials face many challenges with meeting projected enrollment and retention goals. A study’s recruitment materials and messaging convey necessary key information and therefore serve as a critical first impression with potential participants. Yet study teams often lack the resources and skills needed to develop engaging, culturally tailored, and professional-looking recruitment materials. To address this gap, the Recruitment Innovation Center recently developed a Recruitment & Retention Materials Content and Design Toolkit, which offers research teams guidance, actionable tips, resources, and customizable templates for creating trial-specific study materials. This paper seeks to describe the creation and contents of this new toolkit.

We assessed patterns of enteric infections caused by 14 pathogens, in a longitudinal cohort study of sequelae in British Columbia (BC) Canada, 2005–2014. Our population cohort of 5.8 million individuals was followed for an average of 7.5 years/person; during this time, 40 523 individuals experienced 42 308 incident laboratory-confirmed, provincially reported enteric infections (96.4 incident infections per 100 000 person-years). Most individuals (38 882/40 523; 96%) had only one, but 4% had multiple concurrent infections or more than one infection across the study. Among individuals with more than one infection, the pathogens and combinations occurring most frequently per individual matched the pathogens occurring most frequently in the BC population. An additional 298 557 new fee-for-service physician visits and hospitalisations for enteric infections, that did not coincide with a reported enteric infection, also occurred, and some may be potentially unreported enteric infections. Our findings demonstrate that sequelae risk analyses should explore the possible impacts of multiple infections, and that estimating risk for individuals who may have had a potentially unreported enteric infection is warranted.

The recent discovery in Lima's National Museum of History of a sixteenth-century inspection of the royal repartimiento of Yanque Collaguas in the district of Arequipa, has stimulated a search for further important documentation about the region. The investigation was made possible by financial support from the Ford Foundation under its Peruvian program for projects in the social sciences (PA73–807). The project is coordinated by Dr. Franklin Pease G. Y., with the active participation of Dr. N. David Cook, Professor Juan Carlos Crespo (Catholic University, Lima), and Dr. Alejandro Malaga Medina (University of San Agustin, Arequipa).

Knowledge of frontal ablation from marine-terminating glaciers (i.e., mass lost at the calving face) is critical for constraining glacier mass balance, improving projections of mass change, and identifying the processes that govern frontal mass loss. Here, we discuss the challenges involved in computing frontal ablation and the unique issues pertaining to both glaciers and ice sheets. Frontal ablation estimates require numerous datasets, including glacier terminus area change, thickness, surface velocity, density, and climatic mass balance. Observations and models of these variables have improved over the past decade, but significant gaps and regional discrepancies remain, and better quantification of temporal variability in frontal ablation is needed. Despite major advances in satellite-derived large-scale datasets, large uncertainties remain with respect to ice thickness, depth-averaged velocities, and the bulk density of glacier ice close to calving termini or grounding lines. We suggest ways in which we can move toward globally complete frontal ablation estimates, highlighting areas where we need improved datasets and increased collaboration.

Police, like other bureaucratic agencies, are responsible for collecting and disseminating policy-relevant data. Nonetheless, critical data, including killings by police, often go unreported. We argue that this is due in part to the limited oversight capacity of legislative bodies to whom police are accountable. Although many local assemblies lack the means for effective oversight, well-resourced state legislatures may induce transparency from state and substate agencies. This argument is evaluated in two studies of police transparency in the United States. First, we examine the compliance of 19,095 state, county, and municipal police agencies with official data requests over five decades, finding strong positive effects of state legislative capacity on transparency. Second, we examine the accuracy of transmitted data on killings by police, finding that lethality is systematically underreported in states with lower-capacity legislatures. Collectively, our study has implications for research on policing, legislatures, agency control, and analyses of government data.

Childhood trauma is strongly associated with poor health outcomes. Although many studies have found associations between adverse childhood experiences (ACEs), a well-established indicator of childhood trauma and diet-related health outcomes, few have explored the relationship between ACEs and diet quality, despite growing literature in epidemiology and neurobiology suggesting that childhood trauma has an important but poorly understood relationship with diet. Thus, we performed a cross-sectional study of the association of ACEs and adult diet quality in the Southern Community Cohort Study, a largely low-income and racially diverse population in the southeastern United States. We used ordinal logistic regression to estimate the association of ACEs with the Healthy Eating Index-2010 (HEI-10) score among 30 854 adults aged 40–79 enrolled from 2002 to 2009. Having experienced any ACE was associated with higher odds of worse HEI-10 among all (odds ratio (OR) 1⋅22; 95 % confidence interval (CI) 1⋅17, 1⋅27), and for all race–sex groups, and remained significant after adjustment for adult income. The increasing number of ACEs was also associated with increasing odds of a worse HEI-10 (OR for 4+ ACEs: 1⋅34; 95 % CI 1⋅27, 1⋅42). The association with worse HEI-10 score was especially strong for ACEs in the household dysfunction category, including having a family member in prison (OR 1⋅34; 95 % CI 1⋅25, 1⋅42) and parents divorced (OR 1⋅25; 95 % CI 1⋅20, 1⋅31). In summary, ACEs are associated with poor adult diet quality, independent of race, sex and adult income. Research is needed to explore whether trauma intervention strategies can impact adult diet quality.