bluuebunny/crossref_metadata_2025 huggingface dataset:
Constraining self-interacting fermionic dark matter in admixed neutron stars using multimessenger astronomy
Authors: Mariani Mauro , Albertus Conrado , Alessandroni M del Rosario , Orsaria Milva G , Pérez-García M Ángeles , Ranea-Sandoval Ignacio F
Published: November 2023

We investigate the structure of admixed neutron stars with a regular hadronic component and a fraction of fermionic self-interacting dark matter. Using two limiting equations of state for the dense baryonic interior, constructed from piecewise generalized polytropes, and an asymmetric self-interacting fermionic dark component, we analyse different scenarios of admixed neutron stars depending on the mass of dark fermions mχ, interaction mediators mϕ, and self-interacting strengths g. We find that the contribution of dark matter to the masses and radii of neutron stars leads to tension with mass estimates of the pulsar J0453+1559, the least massive neutron star, and with the constraints coming from the GW170817 event. We discuss the possibilities of constraining dark matter model parameters g and y ≡ mχ/mϕ, using current existing knowledge on neutron star estimations of mass, radius, and tidal deformability, along with the accepted cosmological dark matter freeze-out values and self-interaction cross-section to mass ratio, σSI/mχ, fitted to explain Bullet, Abell, and dwarf galaxy cluster dynamics. By assuming the most restrictive upper limit, σSI/mχ < 0.1 cm2 g−1, along with dark matter freeze-out range values, the allowed g–y region is 0.01 ≲ g ≲ 0.1, with 0.5 ≲ y ≲ 200. For the first time, the combination of updated complementary restrictions is used to set constraints on self-interacting dark matter.
Partition function approach to non-Gaussian likelihoods: partitions for the inference of functions and the Fisher-functional
Authors: Kuntz Rebecca Maria , Herzog Maximilian Philipp , von Campe Heinrich , Röver Lennart , Schäfer Björn Malte
Published: November 2023

Motivated by constraints on the dark energy equation of state from a data set of supernova distance moduli, we propose a formalism for the Bayesian inference of functions: Starting at a functional variant of the Kullback–Leibler divergence we construct a functional Fisher-matrix and a suitable partition functional which takes on the shape of a path integral. After showing the validity of the Cramér–Rao bound and unbiasedness for functional inference in the Gaussian case, we construct Fisher-functionals for the dark energy equation of state constrained by the cosmological redshift–luminosity relationship of supernovae of type Ia, for both the linearized and the lowest-order nonlinear models. Introducing Fourier-expansions and expansions into Gegenbauer polynomials as discretizations of the dark energy equation of state function shows how the uncertainty on the inferred function scales with model complexity and how functional assumptions can lead to errors in extrapolation to poorly constrained redshift ranges.
Phased secondary small interfering RNAs inCamellia sinensisvar.assamica
Authors: Suo Angbaji , Yang Jun , Mao Chunyi , Li Wanran , Wu Xingwang , Xie Wenping , Yang Zhengan , Guo Shiyong , Zheng Binglian , Zheng Yun
Published: November 2023

Phased secondary small interfering RNAs (phasiRNAs) in plants play important roles in regulating genome stability, plant development and stress adaption. Camellia sinensis var. assamica has immense economic, medicinal and cultural significance. However, there are still no studies of phasiRNAs and their putative functions in this valuable plant. We identified 476 and 43 PHAS loci which generated 4290 twenty one nucleotide (nt) and 264 twenty four nt phasiRNAs, respectively. Moreover, the analysis of degradome revealed more than 35000 potential targets for these phasiRNAs. We identified several conserved 21 nt phasiRNA generation pathways in tea plant, including miR390 → TAS3, miR482/miR2118 → NB-LRR, miR393 → F-box, miR828 → MYB/TAS4, and miR7122 → PPR in this study. Furthermore, we found that some transposase and plant mobile domain genes could generate phasiRNAs. Our results show that phasiRNAs target genes in the same family in cis- or trans-manners, and different members of the same gene family may generate the same phasiRNAs. The phasiRNAs, generated by transposase and plant mobile domain genes, and their targets, suggest that phasiRNAs may be involved in the inhibition of transposable elements in tea plant. To summarize, these results provide a comprehensive view of phasiRNAs in Camellia sinensis var. assamica.
Small State Diplomacy
Authors: Wivel Anders
Published: November 2023

Small state diplomacy is typically defined in the context of and sometimes opposition to great power diplomacy. Until the end of the Cold War, small states were typically viewed as rule-takers, not rule-makers, and as security consumers, not security producers, in both the academic literature and in diplomatic practice. Since the end of the Cold War, this has changed. Today many studies of small state foreign policy and diplomacy analyze how and under which conditions small states succeed in influencing international affairs and contributing to the maintenance and development of international society. Like great powers, small states seek diplomatic goals reflecting the direct interests of the state such as the maintenance of territorial integrity, advancing prosperity, and protecting citizens abroad in combination with goals aimed as shaping the international environment, e.g., creating peaceful and rule-based international orders and protecting the global commons. However, small states have by definition more limited means than great and middle powers to pursue their diplomatic goals. They have smaller populations leaving them with a smaller tax base for financing diplomats, embassies, and the armed forces. Small states can rarely pursue coercive strategies but must rely on negotiated outcomes. Small domestic markets and the inability to defend themselves against both conventional military threats and threats to societal resilience make small states dependent upon bi- and multilateral agreements. At the same time, they have few resources to influence those agreements. Three characteristics of small state diplomacy reflect how small states seek to meet the challenges following from this predicament. First, small state diplomacy tends to rely heavily on regional and global institutions. International institutions help level the playing field by increasing transparency, creating common rules of behavior for all member states, and giving voice for opportunities. Second, small states tend to focus their diplomatic efforts in narrow diplomatic agendas. They seek to influence selected niches of special importance to the state rather than affecting overall structures and power balances. Finally, small states compensate for their lack of material capabilities by pursuing ideational strategies such as status seeking aimed at increasing their international standing in general or with selected great powers, and norm entrepreneurship aimed at promoting norms of importance to the small state.
Spanish Politics and Government
Authors: Orriols Lluis , Fernández Alvaro
Published: November 2023

Spain became a full democracy in 1977 after nearly four decades of Franco’s dictatorship. Since then, the scientific production on different topics related to Spanish democracy, politics, and government has been extensive, in both Spanish and English language. This article collects some of the major and most influential contributions of this rather broad area of study. We assume that many of those interested in this bibliographic revision may probably be scholars with limited knowledge of the Spanish language. Therefore, this article has prioritized, when possible, the selection of references in English. This article starts by providing some of the most useful overviews on Spanish politics. These essays and edited handbooks represent a good starting point for researchers new to any relevant topic about Spanish politics. Next, we focus on the main political institutions in Spain. We put the focus especially on the executive power, which is the most researched institution by political science scholars in Spain. One of the main defining characteristics of the Spanish political system is its multilevel governance. We dedicate two sections to this topic: the former takes a more institutional approach (multilevel governance) and the latter focuses on the center-periphery political conflict. The subsequent sections delve into the Spanish party system, the main political parties, and the nature and consequences of the electoral system. The Great Recession and Debt Crisis (2008–2014) had notorious consequences on Spanish politics, especially on the party system. New statewide parties emerged, such as Podemos, Ciudadanos and Vox. We dedicate a separate section to this topic, summarizing the extensive production on the political crisis and the rise of new parties since the Great Recession. The final two sections cover relevant research on public opinion and elections at the national, regional, and local levels.
Touristification
Authors: García Hernández María , de la Calle-Vaquero Manuel
Published: November 2023

The term touristification refers to the process of transformation of a place into a tourist space and its associated effects. This transformation operates at the level of both tourist attraction and destination. It implies an adaptation of the place to the visitor and to the interests of the tourism sector. The effects of the transformation process can be positive or negative, and they have a multidimensional character (environmental, landscape, economic, social, or cultural). In contrast to this broad and somewhat neutral meaning, the term has recently become popular with a much more limited meaning and negative connotations. In this sense, there are frequent works that refer to touristification as a process that particularly affects cities and deteriorates the living conditions of their inhabitants. According to this critical perspective, touristification is configured as a process of territorial specialization in the tourist function whose negative impacts far outweigh the positive ones. The academic production on touristification is extensive, although most of the contributions date from after the year 2000. Perhaps for this reason there is still a certain indeterminacy in the use of the term, often associated with other expressions, such as overtourism and tourist gentrification. This article includes chiefly research articles and, to a lesser extent, similar academic formats, which include the term touristification in the title, keywords, or abstract. The references included in this work have been organized in six sections according to their thematic orientation. The first includes the initial references to the term, with a notable predominance of tourism geography of French origin or influence. The second comprises a series of works relating to gentrification and touristification. These papers focus particularly on cities and urban centers and mostly adopt a critical approach. The third section focuses on different case studies on cities, with a special emphasis on southern European cities. The fourth section presents papers that examine in depth some vectors of touristification and associated processes, such as heritagization, urban regeneration, airbnbization, foodification, and tourism-phobia. The fifth section focuses on the new forms of touristification in reference to the urban areas over which the process is advancing. The next section includes references to works on touristification in non-urban areas, such as coastal destinations and rural territories. Finally, a series of references are included that address the subject from a general perspective due to their subject matter or their composition in the form of compendia or special issues of journals.
92. System-wide Implementation of a New Urine Culture to Optimize Diagnostic Stewardship
Authors: Parlich Lisa , Gunn Raymond , Salim Asra , Eberlein Bill , Silkaitis Christina
Published: November 2023

Background

Our healthcare system consists of 8 acute care facilities, each of which utilizes a Urinalysis (UA) with Reflex to Culture laboratory order. With this order, a urine culture is performed automatically if the UA flags as abnormal, thus resulting in overutilization of urine cultures and subsequent identification of urinary tract infections (UTI), including hospital-associated catheter UTI (CAUTI).

Methods

The two largest facilities developed and implemented a new urine order to ensure appropriate utilization of urine cultures on adult critical care (CC) patients: the Urinalysis with Hold for Culture (UA/Hold) order. With this order, a culture would not be completed until a clinician reviewed the UA results, evaluated the need for a culture and then placed an add-on urine culture within 48 hours of the original UA specimen. If the UA was not abnormal, an override reason was chosen for the order, i.e. new urgency, frequency, dysuria, fever, altered mental status, hematuria. Logic existed within this order to not allow a urine culture unless a UA had been performed within the last 48 hours or if a patient was neutropenic, pregnant or undergoing a urological procedure.

Results

From February 2021 to February 2022, the two facilities who implemented the order avoided a total of 485 cultures (Table 1). These two sites also experienced a decrease in CAUTIs compared to the year prior to implementation. The UA/Hold order resulted in a meaningful reduction in CAUTI rates since urine culture orders were only placed on patients that clinically needed them.

Due to the success of the new order, it was expanded to five additional facilities and their CC patient populations in December 2022. Data collected January-March 2023, demonstrates the effectiveness of the implementation, as zero CAUTIs have been reported from CC patients at any of the five hospitals. In the 12 months prior to implementation, 21 CAUTIs had been reported. Overall, 27 cultures were avoided (Table 2).

Conclusion

With exceptional results from the first three months since implementation, the months to come show promise for significant culture and CAUTI reduction across the system and provides opportunity to expand the order to non-critical care units as well.

Disclosures

All Authors: No reported disclosures
97. The Utilization of Echocardiography in Children with Staphylococcus aureus Bacteremia
Authors: Bui Richard , Vallejo Jesus G , Kaplan Sheldon L , McNeil Jonathon C
Published: November 2023

Background

Among children with Staphylococcus aureus bacteremia (SAB) the most common focus of infection is musculoskeletal with infective endocarditis (IE) being relatively rare. Echocardiography (“echo”) is routinely performed in adults with SAB with rates of IE as high as 25%. We evaluated the utility of echo in the setting of SAB in children at a tertiary children’s hospital.

Methods

Children (< 18 years-old) with at least one blood culture positive for S. aureus from 2019-2021 were identified from an ongoing surveillance study at Texas Children’s Hospital in Houston, TX. Medical records were reviewed for all subjects. For this study, we aimed to define the frequency and clinical correlates of a) the utilization of echo and b) evidence of echo-positive IE. Echo evidence of IE was based on the Duke criteria.

Results

331 cases of SAB were identified in children with a median age of 4.9 years. Medical comorbidities were present in 58% of subjects. Musculoskeletal infections were the most common diagnoses followed by CLABSI (Figure 1). 22.1% of infections were due to MRSA. The median duration of bacteremia was 1 day (IQR: 1-2). Echo was performed in 140 (42.3%) subjects. Those who underwent echo had a higher degree of medical complexity, particularly congenital heart disease (CHD, Figure 2), and had a longer duration of bacteremia (median 2 vs. 1 day, p=0.01). Four subjects underwent transesophageal echo. Nine subjects met Duke echo major criteria for IE (6.4%, Figure 3). Subjects with echo-positive IE were more likely to have CHD than those without (66.7% vs. 20.6%, p=0.006); duration of bacteremia or fever among those with and without echo positive IE were not significantly different. Among subjects with CHD and SAB, 15.6% had echo diagnosed IE. 4/9 subjects with vegetations had a single day of SAB.

Figure 2A. Depicts select clinical characteristics with respect to their frequency among subjects who did or did not undergo echocardiogram. Figure 2B. Demonstrates the relative proportion of cases with community-associated, community-onset healthcare-associated and hospital-associated infection.

The figure illustrates select clinical characteristics for subjects with echocardiogram confirmed infective endocarditis (IE)

Conclusion

While a large proportion of children with SAB at our center underwent echo, the frequency of IE by imaging was approximately 6%. Children with CHD are at high risk for IE, however, identifying other children who would benefit the most from echo in the setting of SAB is challenging. Notably, even with short durations of SAB, IE was documented in children with comorbidities. Further multicenter work with very large sample sizes is needed to optimize echo use in children with SAB.

Disclosures

Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria Jonathon C. McNeil, MD, Allergan: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support
99. Predictive model for serious bacterial infections in infants less than 90 days of age based on clinical data and a combination of high-threshold inflammatory biomarkers
Authors: Dabaja-Younis Halima , Makhoul Nadeen , Abu Shqara Rozeen , Damouni Shalabi Ranaa , Reiner-Benaim Anat , Green Green Manfred S , Kassis Imad
Published: November 2023

Background

Serious bacterial infection (SBI) is a life-threatening condition affecting infants less than 90 days of age, and prompt differentiation from non-bacterial infection (NBI) is crucial. Recent guidelines recommend a combination of low-threshold inflammatory biomarkers that need further validation. The aim of this study is to develop predictive models for SBI in infants < 29 days and in infants aged 29-90 days. The study uses detailed clinical data and inflammatory biomarkers with high thresholds.

Methods

This retrospective cohort study was conducted between 2010 and 2019 in a tertiary referral hospital in northern Israel. The study included previously healthy and term infants < 90 days of age who were admitted to the pediatric units of the hospital with febrile illnesses. SBI was defined as bacteremia, meningitis, or urinary tract infection, while NBI was defined as absence of signs of bacterial infection. Detailed clinical and laboratory data were collected for each of the two age groups.

Chart flow of infants included in the study

a Serious bacterial infection, b Non-bacterial infection, c Urinary tract infection, d Respiratory viruses including Respiratory Syncytial Virus, Adenovirus, Influenza A, Influenza B, Parainfluenza, Human Metapneumovirus. Abbreviations: EBV Epstein bar virus, CMV- Cytomegalovirus

Results

A total of 1250 infants met the inclusion criteria, of whom 515 (41.2%) were < 29 days old and 735 (58.8%) were between 29 and 89 days old. In the younger group, 95 (18.4%) had SBI. Risk factors for SBI were diarrhea, absolute neutrophil count (ANC) > 7,500mm3 and CRP > 3mg/dL. Viral symptoms in family members proved to be protective. In the older group, 111 (15.1%) had SBI. Risk factors for SBI were ANC > 7,500mm3 and CRP > 3mg/dL, while male sex, viral symptoms in family members and diarrhea were protective. The study developed a predictive model, the "NeoSBIscore", based on the above predictors, focal infection on physical examination or abnormal urinalysis. The model showed a sensitivity of 94.7% and a negative predictive value (NPV) of 96.9% in infants younger than 29 days and a sensitivity of 93.7% and a NPV of 96.2% in the older group. Only cases with urinary tract infections or bacteriuria were missed in both age groups.

"NeoSBIscore" model to identify infants admitted with febrile illness and at increased risk for serious bacterial infection.

Conclusion

The "NeoSBIscore" model successfully identified infants with SBI, and the use of higher-threshold inflammatory biomarkers did not result in missed cases of SBI, with the exception of a few cases with UTI or bacteriuria. However, external validation is required before this model can be used in clinical practice.

Disclosures

All Authors: No reported disclosures
976. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Analysis of Intravenous Fosfomycin for Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Wangchinda Walaiporn , Pogue jason M , Thamlikitkul Visanu , Leelawattanachai Pannee , Koomanachai Pornpan , (Amit) Pai Manjunath
Published: November 2023

Background

Intravenous (IV) fosfomycin is increasingly used globally for treatment of infections due to multidrug-resistant Gram-negative bacteria (GNB). This study aimed to determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function.

Methods

Eligible patients were adults ≥ 18 years who were treated with IV fosfomycin 2-4 g every 6-8 hours. Five serial blood samples were collected after the 4th dose of fosfomycin and concentrations were measured and modeled by population PK analysis. Monte Carlo simulations were conducted to evaluate the probability of target attainment (PTA) of different dosages using species-specific 1-log10 kill targets (AUC24h/MIC of 98.9, 21.5, and 28.2 for E. coli, K. pneumoniae, and P. aeruginosa, respectively). The kidney function adjusted dosing regimens for E. coli are proposed by using the lowest dose that can achieve ≥ 90% PTA at an MIC of 32 (EUCAST breakpoint) and 64 µg/mL. The highest MIC values at which selected doses provide ≥ 90% PTA for K. pneumoniae and P. aeruginosa were also analyzed.

Results

A total of 138 plasma samples from 28 patients were included. The model was best described by a 1-compartment model with linear elimination. Significant covariates in final model were creatinine clearance and male sex on clearance (CL), and body weight on volume of distribution (V). The parameter estimates were CL of 0.65 ± 0.1 L/h, and V of 12.59 ± 0.8 L. The PTA of simulated dosages for E. coli are shown in Figure 1. For MIC ≤ 32 mcg/mL, a dosage of 12 g/day achieved ≥ 90% PTA for CLCR 90-120 ml/min. For MIC ≤ 64 µg/mL, a dosage of 24 g/day was needed. The proposed kidney function adjusted dosing regimens for E. coli are shown in Table 1. The highest MIC values of K. pneumoniae and P. aeruginosa where these doses provide ≥ 90% PTA were 128 and 256 µg/mL, respectively.

Conclusion

A dosage of 12 g/day of fosfomycin is required for E. coli at EUCAST susceptible breakpoint in patients with normal renal clearance and dose adjustments are needed for patients with renal insufficiency.

Disclosures

jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant
1031. Can We Safely Reduce Unnecessary Blood Cultures in Patients with Suspected Infection in the Emergency Department? The PredictED Study to Develop and Validate a Bacteremia Prediction Model
Authors: Kaal Anna , Meziyerh Soufian , Dane Martijn , Kolfschoten Nikki , Steyerberg Ewout W , van Nieuwkoop Cees
Published: November 2023

Background

Blood cultures are commonly used at emergency departments (EDs), while only 5-10% yields a relevant pathogen. We aimed to develop an automatable prediction model in ED patients with suspected bacteremia. This may reduce the use of blood cultures and prevent potential harm from false-positive blood cultures, while minimizing the risk of missing positive cultures.

Methods

In this observational study, we included consecutive adult patients who had a blood culture taken at the ED of the Haga Teaching Hospital, the Netherlands, for a one-year period. Demographics, laboratory, and outcome data were collected from electronic patient records. We defined 23 candidate predictors for our “full model”, of which nine were used for the "basic" model because they are readily automatable (Table 1). Regression analysis with the Least Absolute Shrinkage and Selection Operator was used to define the model. Bootstrapping was performed for internal validation, including imputation of missing values. We assessed discriminative performance using the C-statistic and calibration using the calibration intercept and slope. Clinical utility was assessed by sensitivity, specificity, negative and positive predictive values and decision curves.

Results

We included 2111 unique patients; mean age 63 years and 46% male. 272 patients had true positive blood cultures (13%); 79 patients (3.7%) had contaminated blood cultures. Our basic model included 8 predictors: age, systolic blood pressure, heart rate, breathing frequency, temperature, Glasgow coma score, C-reactive protein, procalcitonin. The corrected C-statistic was 0.81 (95% CI 0.79-0.83). The full model additionally included recent antibiotic use, indwelling vascular catheter, chills, and suspected infection site. The corrected C-statistic was 0.87 (95% CI 0.85-0.88). Calibration was good for both models. Sensitivity for bacteremia was 97.4% in the basic model, saving 18% of blood cultures (Table 2). The full model could save 26% of blood cultures while maintaining a sensitivity of 98.5% (Table 3).Figure 1.Decision curve analysis

Conclusion

The proposed bacteremia prediction models are designed for easy implementation in electronic patient records and can reduce unnecessary blood cultures. Further external validation is needed before implementation in clinical practice.

Disclosures

All Authors: No reported disclosures
1036. Reporting of SARS-CoV-2 testing results among PEPFAR and non-PEPFAR countries in Sub-Saharan Africa during the first year of the COVID-19 pandemic
Authors: Johnson Benjamin C , Holmes Charles B
Published: November 2023

Background

The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) is the largest global health program dedicated to addressing a single disease. In its first ten years, PEPFAR invested one-fifth of country budgets on governance and health systems strengthening, including laboratories, surveillance networks, and long-term training of health care workers. In addition to furthering the HIV response and promoting the sustainability of health programs, it has been argued these investments built capacity to respond to novel public health threats such as SARS-CoV-2.

Methods

Testing data from 1/1/2020 through 2/17/2021 were downloaded from Our World in Data, an online database that collates information from national and international health agencies. These data were cross-referenced against publicly reported testing totals from Africa CDC and the World Health Organization. The data set did not include testing reported by governments through non-machine-readable formats such as social media or press releases. PEPFAR data were drawn from PEPFAR.gov.

Results

Of the 18 countries in sub-Saharan Africa (SSA) that reported testing data one year into the pandemic, 16 (88.9%) were PEPFAR countries (Table 1). Among PEPFAR countries in SSA, 16 of 27 countries (59.3%) reported SARS-CoV-2 tests performed, compared with 2 of 21 non-PEPFAR countries (9.5%, OR = 13.8). Among countries that reported testing, PEPFAR countries had a per-capita testing rate nearly 3 times that of non-PEPFAR countries (28.7 tests per 1,000 people vs. 9.6 tests per 1,000 people), suggesting greater testing capacity. PEPFAR countries reported higher COVID-19 case rates, likely due to increased testing, however this could also be due to regional differences in incidence (Table 2). Mean GDP per capita was 62% higher in non-PEPFAR SSA countries, making it unlikely that financial resources alone account for the observed differences.Figure 1.Countries that have received PEPFAR funding and countries that reported SARS-CoV-2 testing totals during the first year of the coronavirus pandemicTable 1.Reporting of SARS-CoV-2 testing in sub-Saharan Africa among PEPFAR and non-PEPFAR countries 1 year into the COVID-19 pandemicTable 2.COVID-19 indicators and characteristics of PEPFAR and non-PEPFAR countries in sub-Saharan Africa

Conclusion

PEPFAR countries in SSA were more likely than non-PEPFAR countries to report SARS-CoV-2 testing during the first year of the COVID-19 pandemic and also reported higher per-capita testing rates. This further supports anecdotal evidence that PEPFAR’s historical investments in health systems strengthened local capacity to respond to non-HIV public health emergencies such as COVID-19.

Disclosures

All Authors: No reported disclosures
1105. Clinical outcomes in non-pregnant adults aged ≥18 years hospitalized with laboratory-confirmed RSV infection, 12 U.S. states, October 2014–April 2022
Authors: Melgar Michael , Whitaker Michael , Daily Kirley Pam , Alden Nisha B , Kim Daewi , Openo Kyle P , Brooks Alicia , Leegwater Lauren , Bye Erica , Pacheco Francesca , Barney Grant , Popham Kevin , Sutton Melissa , Talbot H Keipp , Chatelain Ryan , Havers Fiona P
Published: November 2023

Background

Respiratory syncytial virus (RSV) is an important cause of respiratory illness and hospitalization in older adults and adults with certain underlying medical conditions. With novel RSV vaccines in development, it is critical to identify adults at increased risk of severe illness.

Methods

Population-based surveillance was conducted through the RSV Hospitalization Surveillance Network (RSV-NET) over 8 seasons (2014–2022) across 75 counties in 12 states. We included non-pregnant adults (≥ 18 years) residing in the RSV-NET catchment area who were hospitalized with laboratory-confirmed RSV infection (clinician-directed testing) during each season (October–April, except 2020–2021, which spanned October 2020–September 2021). Demographic and outcomes data (all seasons) and underlying medical conditions (October 2014–April 2018) were abstracted from medical records. We calculated percentages of adults with intensive care unit (ICU) admission, mechanical ventilation (MV), and in-hospital death, stratified by demographic characteristics. We calculated age-adjusted percentages with these outcomes, stratified by underlying conditions.

Results

We identified 13,080 RSV-associated hospitalizations among adults; 61.9% were aged ≥ 65 years (Table 1). ICU admission was recorded in 18.6%, MV in 7.2%, and in-hospital death in 4.2%. Most in-hospital deaths (54.1%) occurred among adults aged ≥ 75 years. Among adults 18–49 years, immune compromise (34.8%) and asthma (29.8%) were the most frequent underlying conditions (Figure). Adults with non-asthma chronic lung disease (CLD) and with cardiovascular diseases had the highest age-adjusted percentages of in-hospital death (Table 2). Adults with non-asthma CLD had the highest age-adjusted percentages of ICU admission and MV.

Conclusion

Among adults with RSV-associated hospitalization, older age and cardiopulmonary conditions were associated with severe illness. Hospitalized young adults more likely had immune compromise or asthma. This study was limited by clinician-driven testing, which likely under-detected RSV-associated hospitalizations. Older adults and adults with cardiopulmonary and immune compromising conditions may benefit from RSV vaccination when licensed products become available.

Disclosures

All Authors: No reported disclosures
1168. Cost-effectiveness of high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccine for older people in a country with high influenza vaccination rate
Authors: Nham Eliel , Seong Hye , Hyun Hakjun , Yoon Jin Gu , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Kim Eugene , Choi Leejung , Lee Jung-Min , Song Joon Young
Published: November 2023

Background

The high-dose quadrivalent formulation (QIV-HD) has shown improved protection against influenza and its complications in older adults. We aimed to evaluate the cost-effectiveness of QIV-HD compared with QIV-SD among Korean adults aged ≥ 65 years in reducing influenza-related disease burden.

Methods

We evaluated the 2016/2017 and 2017/2018 seasons and their average values using a static decision tree model. For the main analysis, hospitalization was defined as cardiorespiratory disease-related. The difference in efficacy between standard-dose (SD) and high-dose (HD) was calculated based on the results of a clinical trial comparing Fluzone® High-Dose Vaccine and Fluzone® Vaccine in older adults. Incremental cost-effectiveness ratios (ICERs) were assessed from the healthcare system perspective. A discount rate of 4.5% was applied to life-year-gained (LYG) values and utilities. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economic sources of uncertainty.

Results

In the analysis of the 2017/2018 season, the QIV-HD strategy generated an excess of 0.003953 quality-adjusted life-years (QALYs) compared with QIV-SD. The ICER was 6,467.56 USD/QALY. For the 2016/2017 season, QIV-HD caused an excess of 0.003272 QALYs and ICER was 7,902.46 USD /QALY. From the average data of the two seasons, an excess of 0.003561 QALYs were generated and the ICER was 7,190.44 USD/QALY. In the one-way sensitivity analysis, the parameters with the greatest impact on the results were the relative VE of QIV-HD vs. QIV-SD against influenza-associated hospitalization. PSAs were conducted for the 2016/2017 and 2017/2018 seasons, with the cost of the QIV-HD vaccine fixed at 50,000 KRW (40.48 USD) or 65,000 KRW (52.62 USD). The results showed that for a WTP threshold of 24,692.36 USD/QALY, the probability that QIV-HD is a cost-effective option for the Korean health system is 100% in all seasons and QIV-HD vaccine costs considered.

Conclusion

From the healthcare system perspective, QIV-HD was a more cost-effective vaccination option in reducing influenza-related disease burden and healthcare costs in Koreans aged ≥ 65 years compared with QIV-SD.

Disclosures

Hee Jin Cheong, M.D., Ph.D., Sequiris: Advisor/Consultant Jung-Min Lee, n/a, Sanofi Korea: Stocks/Bonds
1169. Unconjugated Multi-epitope Peptides Adjuvanted with ALFQ Induce Durable and Broadly Reactive Antibodies to Human and Avian Influenza Viruses
Authors: Rikhi Nimisha , Sei Clara J , Rao Mangala , Schuman Richard F , Kroscher Kellie , Matyas Gary R , Muema Kevin , Lange Camille , Assiaw-Dufu Aba , Hussin Elizabeth , Jobe Ousman , Alving Carl R , Fischer Gerald W
Published: November 2023

Background

Traditional influenza vaccine production often leads to mismatch due to antigenic drift, thereby reducing protection. Alternate vaccine strategies that are peptide-based, nanoparticle-based or nucleic acid-based are being developed. Composite multi-epitope peptides provide a cost-effective and easily scalable strategy towards a universal influenza vaccine. In this study, we demonstrate that unconjugated, multi-epitope peptides formulated with the highly potent adjuvant Army Liposome Formulation with QS-21 (ALFQ) generate broadly reactive durable antibodies to human and avian influenza viruses when administered intramuscularly or intradermally.

Methods

ICR mice were immunized with an unconjugated composite influenza peptide vaccine comprising HA+NA (Flu Pep11) and Matrix (M1/M2/M2e)+T-cell epitope (Flu Pep5906) formulated with ALFQ. A low-dose (1 µg) and high-dose (20 µg) of vaccine was administered intramuscularly or intradermally. Isotype-specific IgG titers to composite peptides, individual epitopes, and multiple strains of influenza A (H1N1, H3N2, H5N1), and B (Yamagata, Victoria) were analyzed by ELISA. Neutralizing titers against Group 1 and Group 2 viruses were determined using microneutralization assay.

Results

A robust IgG1 and IgG2b antibody response was seen at day 21 post primary immunization and remained steady for all groups up to day 200 (duration of study). IgG2a and IgG3 titers were also generated. Antibodies recognized multiple strains each of human and avian influenza A and influenza B virus subtypes, 200 days post primary immunization, and were comparable between doses and routes. Strong neutralizing titers were shown against Group 1 and 2 influenza viruses.

Conclusion

An unconjugated peptide vaccine comprising multiple highly conserved epitopes of HA, NA and Matrix formulated with ALFQ adjuvant and administered intramuscularly or intradermally, generated broad and durable antibodies to human and avian influenza viruses. Induced antibodies neutralized seasonal and pandemic influenza strains. These composite peptides adjuvanted with ALFQ generate durable and broad immunity and provide a cost-effective and easily scalable strategy that moves us closer to a universal influenza vaccine.

Disclosures

All Authors: No reported disclosures
1174. Impact of an Electronic Antibiotic Time-out Best Practice Alert on Antibiotic Use and Prescribing Behavior in Hospitalized Patients
Authors: Ackley Tyler , Kuti Joseph L , Bilinskaya Anastasia , Linder Kristin E , Dempsey Casey J
Published: November 2023

Background

Antibiotic time-outs (ATOs) are an evolving stewardship strategy capable of widespread impact with relatively low perceived personnel effort. ATO-based interventions have been shown to improve the rates of antibiotic de-escalation and increase the likelihood of antibiotic optimization. In August 2022, Hartford HealthCare implemented a 72-hour ATO best practice alert (BPA) within the electronic medical record (EMR). Herein, we evaluated the impact of this intervention on antibiotic use and describe behaviors associated with alert prompting.

Methods

This is a multi-center, quasi-experimental, retrospective chart review of admitted patients receiving empiric antibiotics for > 72 hours. An ATO alert was designed and embedded within the EMR and set to fire between the hours of 0700 and 1630. On BPA firing, prescribers were prompted to assess for antibiotic modification – a composite including discontinuation, de-escalation, inclusion of stop-date, and transition to oral therapies. Differences in the rate of antibiotic modification and overall antibiotic prescribing patterns for the 10 most frequently utilized antibiotics were compared between a pre-implementation control period (10/1/21 – 10/31/21) and a post-implementation period (10/1/22 – 10/31/22).

Results

A total of 800 patients were included for analysis. There was no significant difference in the rate of antibiotic modification when comparing the pre- and post-implementation cohort (54.5% vs 57.5%, p = 0.433); however, there was a numerically lower rate of antibiotic escalation in the post-cohort (9.5% vs 5.8%, p = 0.062). The duration of antibiotic therapy was longer in the post-implementation cohort (4.7 vs 5.0 days, p < 0.001).

Conclusion

Despite ATO implementation, rates of antibiotic modification were similar between the pre- and post-cohort. Further work to understand the optimal approach to implementing an ATO will be required to improve the impact on antimicrobial therapy.

Disclosures

Joseph L. Kuti, PharmD, bioMeriuex Inc.: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Merck & Co, Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria
1175. Extended Infusion Beta-lactams in Pediatric Patients with Febrile Neutropenia
Authors: Nagel Jerod , Davidge Karen , King Madeleine , Al-Ajmi Abdullah
Published: November 2023

Background

Febrile neutropenia (FN) is associated with a high risk for infections in patients receiving chemotherapy. Mortality estimates in pediatric patients with FN range from 0.4-3%. Extended infusion (EI) of beta-lactam antibiotics leads to improved pharmacodynamic parameters and is associated with enhanced antimicrobial activity. A recent study demonstrated significantly better overall treatment response in adult patients with documented infections and high-risk FN who received EI vs. standard infusion (SI) piperacillin-tazobactam. There are currently no studies evaluating clinical outcomes of EI beta-lactam use in pediatric patients with FN.

Methods

This study was a single-center retrospective cohort study with a time frame between September 2016-September 2022. The primary objective was to assess the time to fever resolution in patients with FN who received EI vs. SI of beta-lactam antibiotics. Secondary objectives included the difference in 30-day mortality and hospital length of stay (LOS) between the EI and SI groups. This study included patients admitted to pediatric hematology, oncology, or BMT services at Michigan Medicine who were (1) diagnosed with FN during hospital admission or admitted for FN following chemotherapy and (2) treated with EI or SI cefepime, piperacillin-tazobactam, or meropenem for at least 48 hours.

Results

A total of 87 patients were included in the study analysis (40 in the EI group and 47 in the SI group). Baseline characteristics were similar between the groups. There was no significant difference in the time to fever resolution for the cohort (48.5 vs 39.1 hours, p=0.373). There were numeric non-significant differences favoring EI for 30-day mortality (0% vs. 4%, p=0.496), and avoiding need to escalate antibiotic therapy due to treatment failure (7.5% vs. 17%, p=0.214).

Conclusion

The small sample size limited the ability to detect differences in time to fever resolution between EI and SI beta-lactams. Although not statistically significant, secondary endpoints showed numerically lower mortality and lower rates of therapy escalation in the EI group.

Disclosures

Madeleine King, PharmD, BCOP, Elsevier, Inc: Board Member
1183. Implementation of a Nursing and Certified Nursing Assistant Antimicrobial Stewardship Competency-Based Educational Module at a Community Health System
Authors: Chandler Elisabeth , Cubillos Ashley L , Ducas Stephanie , Reyes Iraida , Stedcke Janet , Saunders Mary B
Published: November 2023

Background

The 2019 edition of the CDC Core Elements of Hospital Antibiotic Stewardship Programs created a new category of nursing-based interventions to optimize antimicrobial therapy, however many institutions have not yet implemented these actions. Additionally, accrediting bodies such as the Joint Commission are implementing requirements for multidisciplinary competency-based training as a part of updated standards. Nurses and certified nursing assistants (CNAs) play a valuable role in antimicrobial stewardship (AMS). However, awareness and education pertaining to AMS for nurses and CNAs is not consistent across practice settings, nor do standard recommendations for AMS competency-based education exist. This project aimed to implement and evaluate AMS competency-based education for nursing and CNA staff at a large community health system.

Methods

Implementation of a nursing and CNA AMS online learning module was a multi-step initiative within a community health system. A stepwise approach included assessment of key knowledge gaps, development of educational content specific to the user, creation of an engaging module that included patient cases and knowledge assessment questions, and modification of content to fit within an online learning system. A description of the initiative after competency implementation was assessed.

Results

The online learning module was implemented in December 2022, and the analysis was performed in March 2023. A total of 1,671 nurses and 591 CNAs completed the education in the 3-month time frame. The median duration for competency completion was 26 minutes for nurses (expected duration 30 minutes) and 13 minutes for CNAs (expected duration 20 minutes). Though a passing score of 80% was required for competency completion, 48% of nurses and 74% of CNAs received a passing score of 100%.

Conclusion

Utilizing a standardized online learning system to disseminate an AMS module to nursing and CNA staff achieved a rapid dissemination of AMS competency-based education, enhancing system compliance with CDC recommendations and accrediting organization requirements. Future investigation is needed regarding the impact of educational initiatives on AMS practices for nursing and CNA staff.

Disclosures

All Authors: No reported disclosures
1191. The Implementation of Nasal MRSA PCR for Pneumonia and Association with Antibiotic Use and Clinical Outcomes
Authors: Fenlon Luke A , Fong Karen , Spivak Emily S , Imlay Hannah
Published: November 2023

Background

Nasal MRSA PCR testing has been successfully implemented at many centers and limits vancomycin exposure among hospitalized patients with pneumonia. There are few studies of a Best Practice Alert (BPA) to direct nasal MRSA PCR use and vancomycin de-escalation in the absence of other stewardship oversight. On 1/2/2020, nasal MRSA PCR and a BPA were implemented at our institution. Providers ordering vancomycin for patients with an indication of pneumonia or undifferentiated sepsis were directed to order a nasal MRSA PCR and recommended to stop vancomycin if negative (Figure 1). Our aim was to examine the impact of BPAs implementation on vancomycin duration among patients with suspected pneumonia.

Methods

A retrospective chart review was conducted among hospitalized patients without prior MRSA PCR performed during their admission who had a listed indication of pneumonia or sepsis at the time of vancomycin order. Patients were categorized into “pre” (9/17/2018 – 1/1/2020) and “post” (1/2/2020 – 3/20/2021) cohorts based on date of vancomycin order. Demographics, comorbidities, and antibiotic duration were electronically extracted. Uni- and multivariable logistic models were used to examine the proportion of patients in the pre and post cohorts whose vancomycin was stopped within 24 hours of initial order.

Results

A total of 2,195 patients were included, 1210 in the pre-intervention and 985 in the post-intervention cohort. After BPA implementation, 771/985 (78%) patients received a nasal MRSA PCR. Vancomycin was discontinued within 24 hours after initiation in 384/1210 (32%) patients pre-intervention and 559/985 (57%) patients post-intervention (adjusted OR 2.92 [95% CI 2.44 – 3.49], p < 0.001) (Table 1). Although “high risk” patient factors (e.g. need for mechanical ventilation) were associated with longer durations, vancomycin duration was significantly shorter in the post-implementation cohort for all “high risk” sub-groups (Figure 2).

Conclusion

BPA directed nasal MRSA PCR testing and vancomycin de-escalation effectively shortened duration of therapy among patients with suspected pneumonia. Utilizing a BPA directed approach can improve decision efficiency and allow valuable stewardship team resources to be allocated elsewhere.

Disclosures

All Authors: No reported disclosures