Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

Therapeutic drug monitoring of flecainide in children using plasma concentration measurements is undertaken by some clinicians. There is very little published evidence surrounding factors which influence plasma flecainide concentration, particularly in paediatric populations. We undertook a retrospective study of 45 children receiving flecainide to identify factors that influence its plasma concentration. Patients receiving a dose of 6 mg/kg/day had a higher mean plasma flecainide concentration than those receiving lower doses. Younger age and lighter weight were also associated with higher plasma flecainide concentrations. Children aged younger than 1 year receiving flecainide three times a day had a higher mean plasma flecainide concentration than older children who received flecainide twice a day. All supratherapeutic levels occurred in children aged less than 1 year who were receiving flecainide three times a day. Supratherapeutic levels were more common in those receiving 6 mg/kg/day while subtherapeutic levels were more common in those receiving 2 mg/kg/day. A supratherapeutic level did not correlate with adverse effects or clinical toxicity. Our results would suggest the need for a change of practice from prescribing flecainide at a frequency of three times a day in children aged younger than 1 year to twice a day in line with other ages.

In this large, retrospective cohort study, we used administrative data to evaluate nonpregnant adults with group B Streptococcus (GBS) bacteriuria. We found greater all-cause mortality in those with urinary tract infections compared to asymptomatic bacteriuria. Differences in patients’ baseline characteristics and the 1-year mortality rate raise the possibility that provider practices contribute to differences observed.

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

The remarkable archaeological record of Neolithic Orkney has ensured that these islands play a prominent role in narratives of European late prehistory, yet knowledge of the subsequent Bronze Age is comparatively poor. The Bronze Age settlement and cemetery at the Links of Noltland, on the island of Westray, offers new evidence, including aDNA, that points to a substantial population replacement between the Late Neolithic and Bronze Age. Focusing on funerary practice, the authors argue for interconnecting identities centred on household and community, patrilocality and inheritance. The findings prompt a reconsideration of the Orcadian Bronze Age, with wider implications for population movement and the uptake of cultural innovations more widely across prehistoric north-western Europe.

Social media platforms allow users to share news, ideas, thoughts, and opinions on a global scale. Data processing methods allow researchers to automate the collection and interpretation of social media posts for efficient and valuable disease surveillance. Data derived from social media and internet search trends have been used successfully for monitoring and forecasting disease outbreaks such as Zika, Dengue, MERS, and Ebola viruses. More recently, data derived from social media have been used to monitor and model disease incidence during the coronavirus disease 2019 (COVID-19) pandemic. We discuss the use of social media for disease surveillance.

Background: Group B Streptococcus (GBS) can cause life-threating invasive infections, yet GBS is also a normal component of the intestinal and genitourinary tract. Although it is regarded as a potential urinary pathogen, the morbidity and mortality associated with recovery of GBS from urine cultures of nonpregnant adults is not well understood. We evaluated characteristics and mortality among nonpregnant adults with urine cultures that grew GBS. Methods: Using administrative data from the Veterans’ Healthcare Administration (VHA), we conducted a retrospective cohort study of VA healthcare system users from January 1, 2008, through December 31, 2017, with monomicrobial urine cultures growing ≥100,000 colony-forming units of GBS. Urinary tract infection (UTI) cases were defined as urinalysis positive for leukocyte esterase and pyuria (≥10 white blood cells), an International Classification of Diseases (ICD) code for UTI, and an antibiotic prescription. Cases with colonization were defined as negative for leukocyte esterase and pyuria, no ICD code for UTI, and no antibiotic prescription. Cases not meeting either definition were deemed unclassifiable. We compared demographics, comorbidities, and all-cause mortality among these 3 groups. Results: Over the 10-year study period, 26,848 veterans had 30,740 urine cultures positive for GBS. Applying the definitions above, there were 2,807 cases of infection, 8,789 cases of colonization, and 15,252 cases that were unclassifiable. Patients with a GBS UTI were slightly older compared to those who were colonized, with a higher Charlson comorbidity index and greater burden of chronic renal disease (Table 1). Individuals with infection versus colonization had 30-day mortality rates of 1% and 0%, respectively, and 1-year mortality rates of 9% and 4%, respectively (Figure 1). Conclusions: The association of a greater burden of illness among veterans who met our definition of UTI compared to colonization might be more reflective of providers’ responses to patients with chronic medical conditions rather than a difference in GBS as a cause of UTI. Overall, the prospect of a urine culture that grows GBS does not appear to be associated with adverse long-term outcomes.

Funding: No

Disclosures: None

Table 1.

Figure 1.

Background: The influence of increased use of telehealth during the emergence of COVID-19 on antibiotic prescriptions in outpatient settings is unknown. The VA Northeast Ohio Healthcare System has 13 community-based outpatient clinics (CBOCs) that provide primary and preventive care. We assessed changes in antibiotic prescriptions that occurred as care shifted from in-person to telehealth visits. Methods: Using VHA administrative databases, we identified all primary care CBOC visits between January 1, 2019, and December 31, 2020, that included a diagnosis for an acute respiratory infection (ARI), a urinary tract infection (UTI), or a skin or soft-tissue infection (SSTI), excluding visits with >1 of these diagnoses or with additional infectious diagnoses (eg, pneumonia, influenza). We summarized the proportion of telehealth visits and the proportion of patients prescribed antibiotics at quarterly intervals. We specifically assessed outpatient visits from April to December 2019 compared to the same months in 2020 to account for seasonality while analyzing diagnosis and antibiotic trends in the emergence of the COVID-19 pandemic. Results: The patients receiving care in April–December 2019 compared to April–December 2020 were similar (Table 1). From April through December 2019, 90% of CBOC primary care visits with a diagnosis for ARI, UTI, or SSTI were in-person, and antibiotics were prescribed at 63%, 46%, and 65% of visits in either modality, respectively (Figure 1). From April through December 2020, only 33% of CBOC primary care visits for ARI, UTI, and SSTI were in person, and antibiotics were prescribed at 46%, 38%, and 47% of visits in either modality, respectively. Comparing April–December in 2019 and 2020, the number of CBOC visits for ARI fell by 76% (2,152 visits to 509 visits), with a more modest decline of 20% and 35% observed for UTI and SSTI visits. In-person visits for ARIs and SSTIs were more likely than telehealth visits to result in an antibiotic prescription (Figure 2). Conclusions: Among the CBOCs at our healthcare system, an increase in the proportion of telehealth visits and a reduction in ARI diagnoses occurred after the emergence of COVID-19. In this setting, we observed a reduction in the proportion of visits for ARIs, UTIs, and SSTIs that included an antibiotic prescription.

Funding: Merck

Disclosures: None

Table 1.

Figure 1.

Figure 2.

Background: Outcomes among nursing home residents with asymptomatic compared to symptomatic COVID-19 are not well characterized. We assessed all-cause mortality among Veterans’ Affairs (VA) community living center (CLC) residents; we compared those residents with a negative SARS-CoV-2 test to residents with symptomatic, presymptomatic, and asymptomatic SARS-CoV-2 infections. Methods: We conducted a national retrospective cohort study of CLC residents tested for COVID-19 between March 1 and July 31, 2020, based on data compiled through the VA COVID-19 shared data resource. Among those with a positive SARS-CoV-2 test, residents were considered symptomatic if they had experienced COVID-19 symptoms in the 30 days prior to the test. Residents were considered presymptomatic if they did not experience symptoms in the 30 days prior to testing and developed a fever (>38°C) or required supplemental oxygen within 14 and 60 days, respectively, following the test. Residents were considered asymptomatic in the absence of these pre- and posttest symptoms. Results: From March 1 to July 31, 2020, of 9,052 CLC residents screened for COVID-19, 8,325 (92%) tested negative (Table 1). Among 727 residents with positive tests, 467 (64%) were symptomatic, 88 (12%) were presymptomatic, and 172 (24%) remained asymptomatic. We observed significant differences in the racial makeup of these disease groups. Among CLC residents who were symptomatic or presymptomatic, 176 (32%) of 555 were black compared to 39 (23%) of 172 who were asymptomatic and 1,810 (22%) of 8,325 who tested negative for SAR-CoV-2. All-cause 30-day mortality rates for symptomatic and presymptomatic residents were 25% and 34%, respectively, which exceeded the all-cause 30-day mortality of asymptomatic residents (12%) and residents with a negative test (6%) (Figure 1). Conclusions: More than one-third of CLC residents with COVID-19 were asymptomatic at the time of testing. This finding highlights the importance of vigilant infection prevention and control measures. Our finding that mortality among presymptomatic residents exceeded that of symptomatic residents raises consideration for enhancing supportive care measures, such as supplemental oxygen and mitigation of inflammatory reactions, as a means to reduce mortality among nursing home residents with presymptomatic SARS-CoV-2 infections.

Funding: No

Disclosures: None

Table 1.

Figure 1.

This article considers the origins, both scholarly and personal, of The American Renaissance 1876–1917 exhibition (1979) and the accompanying book catalogue, setting them in the context of architectural and cultural developments in the United States from the 1940s to the 1970s. It traces how the exhibition came about, what it was trying to achieve and how it was received, both at the time and subsequently. It shows that the exhibition was not conceived as an attack on modernism as such or as a work of architectural conservatism. Rather, it was an attempt to rescue from obscurity an entire chapter of American architectural history that had been excluded by the modernising narratives of Henry-Russell Hitchcock, Vincent Scully and others, and to reassess what this architecture might contribute to the present.

Background: Rates of invasive infections caused by caused group B Streptococcus (GBS) are increasing among adults. The burden of noninvasive GBS infections, including pneumonia, has not been well characterized. Here, we compare comorbidities and mortality associated with invasive and noninvasive pneumonia caused by GBS. Methods: Using the Veterans’ Health Administration national data warehouse, we studied a retrospective cohort review of veterans diagnosed with GBS pneumonia between 2008 and 2017. Invasive pneumonia was defined as blood cultures positive for GBS associated with an order for a chest x-ray and an International Classification of Disease (ICD) code for pneumonia. Noninvasive pneumonia was defined as a respiratory culture positive for GBS associated with both an order for a chest x-ray and an ICD code for pneumonia among patients with negative or without blood cultures. Patients with respiratory cultures positive for GBS without either an associated chest x-ray or ICD code for pneumonia were considered colonized. We compared demographics, comorbid conditions, and mortality among patients with invasive and noninvasive GBS pneumonia. Results: Between 2008 and 2017, we detected 706 cases of invasive GBS pneumonia, 1,244 cases of noninvasive GBS pneumonia, and 1,470 cases of respiratory colonization with GBS. Most patients were male (97%), with an average age of 69.0 years (SD, 12.0 years). The prevalence of several comorbid conditions differed between those with invasive and noninvasive disease: diabetes mellitus (61% and 46%, respectively); chronic pulmonary diseases (53% and 65%, respectively); chronic heart disease (58% and 44%, respectively), chronic kidney disease (43% and 27%, respectively). Mortality was similar among those with invasive and noninvasive GBS pneumonia at 30 days (17% and 18%, respectively) and at 1 year (38% and 43%, respectively) (Fig. 1). Conclusions: We identified important differences in underlying comorbid conditions between patients with invasive and noninvasive GBS pneumonia, which may give rise to differences in their clinical presentation. Overall mortality, however, was similar: more than one-third of patients with GBS pneumonia died within 1 year. These findings indicate that noninvasive GBS pneumonia is an important clinical entity.

Funding: This study was supported by Pfizer.

Disclosures: None

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.

Funding: None

Disclosures: None

Over the past decade, a growing interest has developed on the archaeology, palaeontology, and palaeoenvironments of the Arabian Peninsula. It is now clear that hominins repeatedly dispersed into Arabia, notably during pluvial interglacial periods when much of the peninsula was characterised by a semiarid grassland environment. During the intervening glacial phases, however, grasslands were replaced with arid and hyperarid deserts. These millennial-scale climatic fluctuations have subjected bones and fossils to a dramatic suite of environmental conditions, affecting their fossilisation and preservation. Yet, as relatively few palaeontological assemblages have been reported from the Pleistocene of Arabia, our understanding of the preservational pathways that skeletal elements can take in these types of environments is lacking. Here, we report the first widespread taxonomic and taphonomic assessment of Arabian fossil deposits. Novel fossil fauna are described and overall the fauna are consistent with a well-watered semiarid grassland environment. Likewise, the taphonomic results suggest that bones were deposited under more humid conditions than present in the region today. However, fossils often exhibit significant attrition, obscuring and fragmenting most finds. These are likely tied to wind abrasion, insolation, and salt weathering following fossilisation and exhumation, processes particularly prevalent in desert environments.

Over the past decade, the World Health Summit (WHS) has provided a global platform for policy-makers and decision-makers to interact with academics and practitioners on global health. Recently the WHS adopted health security into their agenda for transnational disease risks (eg, Ebola and antimicrobial resistance) that increasingly threaten multiple sectors. Global health engagement (GHE) focuses efforts across interdisciplinary and interorganizational lines to identify critical threats and provide rapid deployment of key resources at the right time for addressing health security risks. As a product of subject matter experts convening at the WHS, a special side-group has organically risen with leadership and coordination from the German Institute for Defense and Strategic Studies in support of GHE activities across governmental, academic, and industry partners. Through novel approaches and targeted methodology that maximize outcomes and streamline global health operational process, the Global Health Security Alliance (GloHSA) was born. This short conference report describes in more detail the GloHSA.

Carbonate glasses can be formed routinely in the system K2CO3–MgCO3. The enthalpy of formation for one such 0.55K2CO3–0.45MgCO3 glass was determined at 298 K to be 115.00 ± 1.21 kJ/mol by drop solution calorimetry in molten sodium molybdate (3Na2O·MoO3) at 975 K. The corresponding heat of formation from oxides at 298 K was −261.12 ± 3.02 kJ/mol. This ternary glass is shown to be slightly metastable with respect to binary crystalline components (K2CO3 and MgCO3) and may be further stabilized by entropy terms arising from cation disorder and carbonate group distortions. This high degree of disorder is confirmed by 13C MAS NMR measurement of the average chemical shift tensor values, which show asymmetry of the carbonate anion to be significantly larger than previously reported values. Molecular dynamics simulations show that the structure of this carbonate glass reflects the strong interaction between the oxygen atoms in distorted carbonate anions and potassium cations.

Schmidt-hammer exposure-age dating (SHD) of boulders on cryoplanation terrace treads and associated bedrock cliff faces revealed Holocene ages ranging from 0 ± 825 to 8890 ± 1185 yr. The cliffs were significantly younger than the inner treads, which tended to be younger than the outer treads. Radiocarbon dates from the regolith of 3854 to 4821 cal yr BP (2σ range) indicated maximum rates of cliff recession of ~0.1 mm/yr, which suggests the onset of terrace formation before the last glacial maximum. Age, angularity, and size of clasts, together with planation across bedrock structures and the seepage of groundwater from the cliff foot, all support a process-based conceptual model of cryoplanation terrace development in which frost weathering leads to parallel cliff recession and, hence, terrace extension. The availability of groundwater during autumn freezeback is viewed as critical for frost wedging and/or the growth of segregation ice during prolonged winter frost penetration. Permafrost promotes cryoplanation by providing an impermeable frost table beneath the active layer, focusing groundwater flow, and supplying water for sediment transport by solifluction across the tread. Snow beds are considered an effect rather than a cause of cryoplanation terraces, and cryoplanation is seen as distinct from nivation.

Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.