bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerodynamic performance of flapping wing with alula under different kinematics of complex flapping motion
Authors: Bao Han , Song Bifeng , Ma Dongfu , Xue Dong
Published: November 2023

The flight of birds is a remarkable feat, and their remarkable ability to fly derives from complex multi-degree-of-freedom flapping motions and small-scale feather structures that have evolved over millions of years. One of these feather structures is the alula, which can enhance the birds’ flight performance at low speeds and large angles of attack. Previous studies on the alula have focused on the steady state. This undoubtedly ignores the unsteady effect caused by complex flapping motion, which is also the most important characteristic of avian flight. Therefore, this paper carries out a study on the effect of different motion modes and motion parameters on the aerodynamic mechanism of the alula. Previous studies found the dominate effect in the lift enhancement is influenced by Reynolds number, stall condition and geometric parameters. After coupling complex flapping motion, aerodynamic characteristics of the flapping wing are greatly influenced by different motion patterns and parameters. For pure plunge motion, both the slot effect and the vortex generator effect of the alula dominate the lift enhancement; while for plunge-twist and plunge-sweep motion, the vortex generator dominates more. At a low plunge amplitude, a low twist amplitude and a low sweep amplitude, the deflection of the alula has a good lift enhancement compared with the baseline wing. Increasing these amplitudes attenuates both the slot effect and the vortex generator effect. The alula can enhance the lift by 10.4% at the plunge amplitude of 25 deg (for pure plunge motion), by 7.9% at the plunge amplitude of 25 deg and twist amplitude of 10 deg (for plunge-twist motion), by 3.3% at the plunge amplitude of 25 deg and sweep amplitude of 15 deg (for plunge-sweep motion). Meanwhile, at a large sweep phase angle, the alula has a better lift enhancement. Increasing the phase angle enhances the vortex generator effect of the alula, and it has an optimal lift enhancement effect of 11% at the phase angle of 180 deg.
Scoping review of carbon pricing systems in forest sector models
Authors: Honkomp Tomke , Schier Franziska
Published: November 2023

Forest-based measures to mitigate climate change are increasingly being acknowledged as options for meeting the global targets of the Paris Agreement. In this context, carbon pricing systems may foster carbon sequestration in forests and harvested wood products. Forest sector models (FSMs) are established simulation instruments for assessing the possible impacts of carbon pricing systems on forest-based mitigation potentials, forestry, and forest product markets. However, the characteristics of the implemented carbon pricing systems differ among these assessment tools. To map and evaluate this variability, we conducted a scoping review of carbon pricing systems in FSMs, following the RepOrting standards for Systematic Evidence Syntheses (ROSES). Drawing on 49 modeling studies, including 351 scenarios, we provide an overview of the state-of-the-art methods for implementing carbon pricing systems in FSMs, discuss technical aspects and uncertainties, and identify possible future research trends. Our results reveal similarities in the types of carbon pricing systems and differences regarding the system boundaries and carbon price-related characteristics of the implemented systems. Geographically, since most studies target either the Northern Hemisphere or the world, we found a lack of in-depth assessments in tropical and boreal countries. Further, additionality, permanence, and leakage of forest-related mitigation measures are addressed using different approaches with varying practicability. Mostly, the observed heterogeneity in the implemented carbon pricing systems can be related to the attributes of pre-existing modeling frameworks. We systematically collect and highlight tools to analyze the role of forest-based mitigation measures in the context of climate commitments and outline carbon pricing policies that could support their implementation. For future studies, the assessment of policy mixes involving carbon pricing and the inclusion of climate change effects on forest growth appear to be crucial for delivering more robust projections of forest-based mitigation potentials and, hence, for increasing the reliability of the forest-based contribution to climate mitigation actions.
Quantifying channel coherence via the norm distance
Authors: Ye Mingfei , Luo Yu , Li Yongming
Published: November 2023

Quantifying the number of resources contained in a physical object has been one of the core topics in the resource theory of coherence. In this paper, we introduce the dynamical coherence measures based on a class of norms in the classical channel setting. It is proved that it satisfies faithfulness, decreases monotonically under the maximally incoherent superchannels, and is convex. Moreover, we show that it satisfies subadditivity under both the composition and tensor product of channels. Especially, the diamond measure as a special case is discussed in detail, it can reduce to trace norm of coherence, satisfies amortization inequality, and can be calculated efficiently using a semidefinite program. In addition, we introduce the creation-coherent diamond measure and find that neither the detection coherence nor the creation coherence of a channel exceeds the coherence of the channel, which does not exceed the purity of the channel. Second, we introduce the corresponding dephasing measure, which is a dynamical coherence measure under the dephasing-covariant incoherent superchannels. Meanwhile, we also introduce the dephasing diamond measure as a special case. Third, we use the dephasing diamond measure to accurately calculate the coherence values of some important noisy channels such as amplitude damping channel, phase damping channel, and depolarizing channel, respectively, and give the sufficient and necessary conditions for an unital qubit channel with a parameter probability vector to be a coherent channel. Finally, the operational interpretation of our diamond measure in the binary channel discrimination task is investigated.
Achieving enhanced tensile properties of polyurethane-multiwall carbon nanotubes nanocomposites
Authors: Gohar Ghulam Abbas , Akhtar Awais , Raza Hassan , Mustafa Ghulam , Fatima Mahreen , Rehman Habib Ur , Aslam Muhammad Waqas , Haq Abrar ul , Manzoor Waqar
Published: November 2023

Polymeric nanocomposites have emerged as a promising class of materials with improved strength, stiffness, and toughness compared to pure polymers. The incorporation of nanoparticles into polymer matrices, such as carbon nanotubes, graphene, clay nanoparticles, and metal oxides, has shown considerable potential for enhancing the properties of the produced nanocomposites. Herein, the influence of filtered multiwalled carbon nanotubes (MWCNTs) on solution-cast polyurethane (PU) nanocomposite is explored. Scanning electron microscopy (SEM), x-ray diffraction (XRD), Raman spectroscopy, thermogravimetric analysis (TGA), and x-rays photoelectron spectroscopy (XPS), respectively, were employed to characterize the morphology, crystal structure, phase, thermal stability, and oxidation states of the samples. MWCNTs with a higher weight% of MWCNTs showcased superior mechanical properties compared to base polymer (PU). The nanocomposite with 1 wt% of MWCNTs and 99 wt% of PU exhibited the highest stress (19.25 N mm−2) and strain (700.22%) among all fabricated samples. Also, Modulus of elasticity (∼25%), Ultimate tensile strength (∼21%), and elongation at break (∼11%) are increased by incorporating 0.5 wt% MWCNTs into PU matrix. The attainment of these remarkable mechanical properties could be attributed to excellent dispersion, interfacial bonding and structural stability of filtered MWCNTs in the nanocomposites.
On the consistency strength of 𝖬𝖬(𝜔₁)
Authors: Dobrinen Natasha , Krueger John , Marun Pedro , Mota Miguel Angel , Zapletal Jindrich
Published: November 2023

We prove that the consistency of Martin’s Maximum restricted to partial orders of cardinality

ω
1

\omega _1

follows from the consistency of

Z
F
C

\mathsf {ZFC}

.
Global well-posedness for Ericksen-Leslie system with zero viscosity
Authors: Zhou Jianfeng
Published: November 2023

We study the global well-posedness of the simplified Ericksen-Leslie system with zero viscosity on the periodic domain

T

2

\mathbb {T}^2

. Precisely, we prove the global existence and uniqueness of smooth solution to Ericksen-Leslie system if the initial data

(

u
0

,
∇

d
0

)

(u_0,\nabla d_0)

is small in

H
4

(

T

2

)
×

H
4

(

T

2

)

H^4(\mathbb {T}^2)\times H^4(\mathbb {T}^2)

. Furthermore, we derive the time decay estimate of

∇
d

\nabla d

in

H
1

(

T

2

)

H^1(\mathbb {T}^2)

.
Safety and efficacy of dual tyrosine kinase 2 inhibitor and monoclonal antibody therapy for psoriasis and psoriatic arthritis
Authors: Guénin Sophie , Andrews Elizabeth , Lebwohl Mark G
Published: November 2023

Deucravacitinib may confer an additive effect in some patients with psoriasis and psoriatic arthritis whose disease is not adequately controlled on systemic monotherapy. This study found that deucravacitinib proved to be a safe adjunctive therapy to patients with refractory disease.
Exacerbation of clinical manifestations of bullous pemphigoid after treatment with dupilumab
Authors: Mariotti Elena Biancamaria , Corrà Alberto , Aimo Cristina , Ruffo di Calabria Valentina , Quintarelli Lavinia , Verdelli Alice , Caproni Marzia
Published: November 2023

The article presents an adverse event that occurred after the induction phase of dupilumab, administered in another country to a patient affected by bullous pemphigoid.
Information content and temporal structure of face selective local field potentials frequency bands in IT cortex
Authors: Sajedin Atena , Salehi Sina , Esteky Hossein
Published: November 2023

Sensory stimulation triggers synchronized bioelectrical activity in the brain across various frequencies. This study delves into network-level activities, specifically focusing on local field potentials as a neural signature of visual category representation. Specifically, we studied the role of different local field potential frequency oscillation bands in visual stimulus category representation by presenting images of faces and objects to three monkeys while recording local field potential from inferior temporal cortex. We found category selective local field potential responses mainly for animate, but not inanimate, objects. Notably, face-selective local field potential responses were evident across all tested frequency bands, manifesting in both enhanced (above mean baseline activity) and suppressed (below mean baseline activity) local field potential powers. We observed four different local field potential response profiles based on frequency bands and face selective excitatory and suppressive responses. Low-frequency local field potential bands (1–30 Hz) were more prodominstaly suppressed by face stimulation than the high-frequency (30–170 Hz) local field potential bands. Furthermore, the low-frequency local field potentials conveyed less face category informtion than the high-frequency local field potential in both enhansive and suppressive conditions. Furthermore, we observed a negative correlation between face/object d-prime values in all the tested local field potential frequency bands and the anterior–posterior position of the recording sites. In addition, the power of low-frequency local field potential systematically declined across inferior temporal anterior–posterior positions, whereas high-frequency local field potential did not exhibit such a pattern. In general, for most of the above-mentioned findings somewhat similar results were observed for body, but not, other stimulus categories. The observed findings suggest that a balance of face selective excitation and inhibition across time and cortical space shape face category selectivity in inferior temporal cortex.
Within- and between-population comparisons suggest independently acting selection maintaining parallel clines in Scots pine (Pinus sylvestris)
Authors: Kujala Sonja T , Avia Komlan , Kumpula Timo A , Kärkkäinen Hanni , Heikkinen Juha , Kärkkäinen Katri , Savolainen Outi
Published: November 2023

Parallel clines in traits related to adaptation in a species can be due to independent selection on a pair of traits, or due to selection in one trait resulting in a parallel cline in a correlated trait. To distinguish between the mechanisms giving rise to parallel adaptive population divergence of multiple traits along an environmental gradient we need to study variation, correlations, and selective forces within individual populations along the gradient. In many tree species, budset timing (BST) forms a latitudinal cline, and parallel clinal variation is also found in other seedling traits, such as first-year height (FYH) and fall frost injury (FFI). In this study, we set up a common garden experiment with open pollinated progeny from natural populations of Scots pine (Pinus sylvestris), with one large sample from single population (500 families) and smaller samples from across a latitudinal gradient. BST, FYH and induced FFI were first measured in a greenhouse. The seedlings were then planted in the field, where survival and height were measured at the age of 9 years as fitness proxies. We compared between- and within-population variation and genetic correlations of these three seedling traits, and estimated selection gradients at the family level in our main population, taking into account the potential effects of seed weight. Between-population genetic correlations between seedling traits were high (0.76–0.95). Within-population genetic correlations in the main population were lower (0.14–0.35), as in other populations (0.10–0.39). Within population, extensive adaptive variation persists in the seedling traits, in line with rather weak selection gradients, yet maintaining the clines. Although our sampling does not cover the whole cline equally, the results suggest that the individual clines in these traits are maintained by largely independently acting selection, which results in fewer constraints in adaptation under changing climate.
Effect of snow cover on the off-host survival of Dermacentor variabilis (Acari: Ixodidae) larvae
Authors: Diyes Chulantha P , Yunik Matthew E M , Dergousoff Shaun J , Chilton Neil B
Published: November 2023

The geographical range of the American dog tick, Dermacentor variabilis (Say), in Canada continues to expand northwards into areas with colder winter temperatures. Understanding what influences the off-host survival of D. variabilis over winter is important for predicting the northern distributional limit of this species. A field experiment was conducted to determine the effect of snow cover on the off-host survival of unfed D. variabilis larvae from a population situated near the northern distributional limit in Saskatchewan, Canada. Ticks were placed in tubes within 1 of 9 field enclosures (tickaria) in early fall. The 9 tickaria were divided into 3 equal treatment groups: no snow cover, natural snow cover (maximum depth of 25 cm) and extra snow cover (maximum depth of 32 cm). Tick survival was measured in mid-winter and in early spring (i.e., ~17 and ~26 wk after start of experiment). The results showed that snow cover had a significant impact on the relative humidity, but not temperature, in the tickaria. Larvae in tickaria with no snow cover had a higher mortality rate (27%) than larvae in tickaria with natural snow cover (6%) or extra snow cover (4%). Although snow cover enhanced off-host survival, many individuals were able to survive in sub-zero temperatures under leaf litter in the absence of continuous snow cover for a period of 108 days. These findings have implications for the construction of predictive models to determine the northern distributional limits of D. variabilis, a species that is an important vector of several pathogens.
Legal Design in Sustainable Antitrust
Authors: Inderst Roman , Thomas Stefan
Published: November 2023

We lay out a roadmap for how the legislator could create a framework of ‘sustainability corridors’ that would allow relying on the ancillary restraints/Wouters doctrine to make antitrust law more accommodating of sustainability considerations. Our analysis goes beyond the general feasibility of such corridors. It discusses different use-cases for such exemptions and methods for assessing the necessity of competitive restraints to achieve a legislatively defined sustainability goal. We show how this avoids the pitfalls of a multigoals approach, under which it would be left to antitrust authorities and courts to reconcile sustainability and competition objectives independent of a legislative specification, whereas out-of-market benefits (externalities) that would escape even a broad consumer welfare approach can still be accounted for. Our proposal sets out specific requirements for such sustainability corridors that ensure that the ensuing antitrust assessment is governed by a strict and quantifiable indispensability test. Specifically, we discuss three such instances: specific sustainability obligations placed on individual firms, which may however require collective actions; specific mandates that are targeted at the respective industry rather than individual firms; and policy objectives that are not targeted at individual firms or industries but provide a metric for the measurement of sustainability benefits (for example, by way of conducting an abatement cost analysis).
102. Assessing ChatGPT Performance in the Brazilian Infectious Disease Specialist Certification Examination
Authors: Chaves Fernandes Alexandre , Varela Cavalcanti Souto Maria Eduarda , Felippe Jabour Thais Barros , Luz Kleber G , Pipolo Milan Eveline
Published: November 2023

Background

Advances in artificial intelligence have the potential to impact medical fields, including the use of natural language processing-based models, such as ChatGPT. The ability of the ChatGPT to provide insightful responses across diverse fields of expertise could assist in medical decision-making and knowledge management processes. ChatGPT has already demonstrated high accuracy in medical examinations such as the USMLE. To explore the potential of this tool in various contexts, our study aimed to evaluate the accuracy of the ChatGPT in the 2022 Brazilian Infectious Disease Specialist Certification Examination.

Methods

We conducted a test to evaluate the performance of GPT-3.5 and GPT-4 on the 2022 Brazilian Infectious Disease Specialist Certification Exam. A theoretical exam, consisting of 80 multiple-choice questions with five alternatives, was used to test performance. The GPT was given a command containing the question statement and alternatives, and a brief comment on the logic behind the answer was requested. Descriptive statistics were used to analyze the absolute performance of the correct answers in the ChatGPT-3.5 and ChatGPT-4 models. In addition, the degree of correlation between answers and performance throughout the test was estimated using Spearman's coefficient and a logistic regression curve, respectively.

Results

Of the 80 questions in the exam, four were excluded because they were invalidated in the final answer key. ChatGPT-3.5 had an accuracy of 53.95% (41/76), whereas ChatGPT-4 had an accuracy of 73.68% (56/76). Spearman's correlation coefficient between the two models was 0.585. There was a slight trend towards improvement in ChatGPT-4 performance throughout the test, as observed in the logistic regression curve.

Comparison of Accuracy between ChatGPT 3.5 and ChatGPT4

The graph shows the percentage of accuracy for the two GPT models. The performance of ChatGPT-4 was superior to ChatGPT-3.5.

Distribution of Correct and Incorrect Responses by ChatGPT-4 in Medical Test Questions

The graph displays the distribution of responses generated by ChatGPT-4. The logistic regression curve shows a slight upward trend, indicating a slight improvement in performance as the questions were answered.

Conclusion

ChatGPT-4 achieved performance above the 60% minimum threshold required for the certification exam. This indicates that it is a promising technology in various fields, including infectious diseases. However, its potential applications and associated ethical dilemmas must be thoroughly assessed. This advancement also highlights the need for medical education to concentrate on developing competence, skills, and critical thinking rather than relying solely on memorization

Disclosures

All Authors: No reported disclosures
1107. Three Year Longitudinal Assessment of Pseudomonas aeruginosa (Pa) Antibiotic Susceptibility in Children with Cystic Fibrosis (CF) in the Era of Modulator Therapy
Authors: Bradley John , Stout Dayna , Akong Kathryn , Fireizen Yaron
Published: November 2023

Background

CF is a genetic disease characterized by chronic lung infection, often with Pseudomonas aeruginosa (Pa). It is widely accepted that increasing antibiotic resistance develops in Pa following repeated antibiotic exposure. With the advent of elexacaftor/tezacaftor/ivacaftor (ETI) modulator therapy, we wished to assess Pa antibiotic resistance to beta-lactam and fluoroquinolone (FQ) antibiotics in both children receiving ETI, and those not eligible for ETI (nonETI) who continue to experience recurrent pulmonary exacerbation (PEx) and require repeated antibiotic treatment.

Methods

We examined current patterns of antibiotic resistance over 3 years for a cohort of 11 children with CF having 5 or more positive sputum cultures for Pa between January 2020-December 2022 obtained from CF clinic and hospital PEx sputum samples. Chart review included: demographic data; dates of PEx/hospitalization; dates of CF clinic visits; dates and results of CF sputum cultures; and antibiotics used and dates for intravenous (IV) and oral (PO) treatment courses.

Results

Six males and 5 females were reviewed (6/11 [54%] were Hispanic), with 3/11 (27%) on ETI therapy (average age 14.6 yr), and 8/11 (73%) not on ETI therapy (average age 11.6 yr). Average age at acquisition of Pa was 10.2 yrs. The average number of cultures yielding Pa over 3 years was 11 for both ETI and nonETI subjects. Average number of IV antibiotic courses was 6 for nonETI, but 0 for ETI subjects, while the average number of oral (PO) FQ courses with ciprofloxacin/levofloxacin was 6 in nonETI, and only 1 in ETI subjects. No increase in antibiotic resistance was noted against any IV antibiotic over 3 years of observation (Table), but of the 9 subjects (both ETI and nonETI) who received PO FQ, 5 (55%) were documented to have at least one nonsusceptible isolate, as shown for one 16 year old nonETI subject (Figure).

Conclusion

Current antibiotic/pulmonary management of children with CF was not associated with an increased risk of IV antibiotic resistance over 3 years of observation despite repeated exposure for PEx (mean of 6 IV antibiotic courses per nonETI subject), but susceptibility to FQ decreased in 55% of those treated over 3 years following repeated FQ oral therapy courses.

Disclosures

All Authors: No reported disclosures
1197. Pharmacist-assisted urine culture review and antimicrobial stewardship interventions in the emergency department: A study from the Middle East Gulf region
Authors: Hisham Mohamed , ElLababidi Rania , Alsalama Fatima , Elrefaei Hazem , Nasef Rama , Khan Muhammad Zeeshan , Souster Timothy
Published: November 2023

Background

Urinary tract infection (UTI) is one of the most frequent reasons encountered for emergency department (ED) visits. The treatment of asymptomatic bacteriuria (ASB) is identified as one of the causes of inappropriate antimicrobial use. We designed the study to evaluate and improve the prescribing practices for UTIs in Cleveland Clinic Abu Dhabi ED. To our knowledge, this is one of the first studies in the Middle East Gulf region which evaluated the impact of pharmacist-assisted urine culture review in the ED.

Methods

A pre-post quasi-experimental study was conducted between September 2021 and July 2022 with a 4-month pre-intervention phase, a 3- month wash-out period, and a 4-month post-intervention phase. The pharmacist-assisted antimicrobial stewardship interventions included distinguishing between UTI and ASB, proper screening through diagnostic stewardship, and rationalizing the need to order urine cultures. The major interventions included appropriate antimicrobial therapy, dosing, frequency, and duration of therapy in compliance with the hospital guidelines. All patients with a negative urine culture, aged ≤ 18 years, or requiring inpatient admission during the same ED visit were excluded from the study. Data were analyzed using Fisher’s exact test.

Results

Three hundred and seventy ED patients were included in the study. Thirty percent of the urine cultures were ordered for patients without urinary signs and symptoms. Escherichia coli was the predominant urinary isolate in our study from both groups, followed by Klebsiella species and Streptococcus agalactiae. Antimicrobials were prescribed for asymptomatic bacteriuria in 5.2 % of patients in the post-intervention group and 21.8 % in the pre-intervention group (P = 0.0001). Readmission to ED for the same complaints within 30 days of the ED visit occurred in 9.8 % of patients in the post-intervention group and 13.2 % in the pre-intervention group (P = 0.3337). All study findings are presented in the tables.Table 1:Characteristics of the pre-and post-intervention groupTable 2:Treatment and outcome of the pre-and post-intervention groupTable 3:Impact of pharmacist-assisted urine culture review in the emergency department

Conclusion

Our study observed higher rates of appropriate culture-direct antimicrobial therapy after implementing the pharmacist-assisted urine culture review and positively impacted clinical outcomes. Additionally, there was a significant reduction in treating asymptomatic bacteriuria.

Disclosures

All Authors: No reported disclosures
1984. Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy
Authors: McComsey Grace A , Sattar Abdus , Albar Zainab , Ansari Gilani Kianoush , Labbato Danielle , Foster Theresa , Ross Eckard Allison
Published: November 2023

Background

Lipohypertrophy (central adipose tissue (AT) accumulation) is a common and significant problem in people with HIV (PWH). Pathogenesis remains elusive; yet, AT abnormalities are key drivers of cardiometabolic co-morbidities in HIV. We aimed to assess effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on AT in PWH with lipohypertrophy.

Methods

We conducted a randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥ 18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥ 25 kg/m2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Computed tomography and whole-body dual-energy X-ray absorptiometry were used to measure area/density in abdominal AT [total (TAT), visceral (TAT), and subcutaneous (SAT)] and body composition [lean body mass (LBM), limb/trunk/total body fat (TBF)], resp. Semaglutide effects were estimated using generalized estimating equations or simultaneous quantile regressions on outcome variables.

Results

108 participants were enrolled (N = 54 semaglutide: median age = 52 years, 70% male, 61% Black, 83% integrase inhibitor). Groups were well-matched at baseline. In unadjusted models, semaglutide group had greater reductions (P < 0.05) in BMI, homeostatic model of insulin resistance (HOMA-IR), trunk fat, TBF (at quantile ≥ 75th), TAT, and SAT with trends (P < 0.1) for limb fat and VAT (Fig 1/Table 1). Semaglutide effects remained significant for BMI, HOMA-IR, trunk fat, TAT, and VAT after adjusting for age, sex, CD4, and ART duration (Table 2); caloric intake was also significant at ≤ 50th quantile. No differences were seen in LBM, AT density, or VAT/TAT ratio. Semaglutide was well-tolerated; serious adverse events were rare.

Conclusion

Semaglutide significantly decreased central fat in PWH with lipohypertrophy, primarily driven by reductions in VAT. Semaglutide may offer an effective treatment to decrease visceral adiposity and reduce co-morbidity risk. Further investigation is needed to determine mechanisms by which reductions in visceral adiposity occur.

Disclosures

Grace A. McComsey, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support
1331. High direct costs caused by Cryptococcal meningitis treated with Amphotericin B deoxycholate in a public hospital in Lima, Peru. 2021-2022
Authors: Vilcarromero Stalin , Luque Arturo , Luarte Norka , Mateo-Pacora Jimmy , Mendo Fernando
Published: November 2023

Background

Cryptococcal meningitis (CM) is a severe disease caused by a ubiquitous fungus that affects both immunocompetent and immunosuppressed people. The treatment of choice includes liposomal amphotericin plus flucytosine; however, in Peru, both medications are not available. Hence, in Peru, CM is usually treated with Amphotericin B deoxycholate, despite adverse events that include longer hospital stays and a higher frequency of complications resulting in higher direct costs. The objective of this study is to evaluate the direct cost of CM in adults in the infectious disease service of the Edgardo Rebagliati Martins National Hospital in Lima, Peru. To do this, the clinical histories of adult patients hospitalized during the 2021 and 2022, and diagnosed by positive culture in the cerebrospinal fluid, were reviewed (Fig 1)

Methods

Nine positive CM cases were identified; only six met the inclusion criteria. Daily hospitalization costs were estimated using published rates of IETSI-ESSALUD, a public employer-based health insurance. Costs for images and laboratory were based on private sector costs.

Positive culture in the cerebrospinal fluid for Cryptococcus sp

Results

Three of the six cases were female and the mean age was 52.6 [39-61]. All six presented headache, nausea and vomiting. Three had HIV infection. All presented renal injury and hematological toxicity (Table 1). Three presented nosocomial infections. The average hospital stay was 66 days [30-90 days] with a total cost for all six patients of USD 35,168. The average direct cost per patient was USD 5,024 with the following distribution: average cost per hospital bed per person: USD 3,584.28; average cost of complete treatment with amphotericin b deoxycholate: USD 119; average cost for laboratory tests was USD 935; average cost for imaging was USD 385 USD (Table 2).

Conclusion

The direct cost for CM treatment with amphotericin B deoxycholate is approximately USD 5,024; as a reference, the minimum monthly salary in Peru is USD 277. This high cost is not due to the drug, which is cheaper for the health system, but due to the long hospital stay and complications that occur. The small sample size is a great limitation; however, it partially reveals financial considerations that should be further and more thoroughly evaluated in the public health system in Peru.

Disclosures

All Authors: No reported disclosures
2150. In Vitro Activity of Cefepime-Taniborbactam and Comparators Against Genotypically Characterized Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) from the United States, 2018-2021
Authors: Wise Mark G , Hackel Meredith , Sahm Daniel F
Published: November 2023

Background

Taniborbactam, a cyclic boronate-based β-lactamase inhibitor with activity against serine-, and NDM & VIM metallo-β-lactamases (MBLs), in combination with the fourth-generation cephalosporin, cefepime, is in development for treatment of complicated urinary tract infections. This study examined the in vitro activity of cefepime-taniborbactam against clinical isolates from the US, with a focus on carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA).

Methods

From 2018-2021, as part of the GEARS Antimicrobial Surveillance Program, 4,220 Enterobacterales and 1,222 P. aeruginosa were collected from 38 clinical sites in the US. MICs of cefepime with taniborbactam fixed at 4 µg/mL and comparators were determined by broth microdilution according to CLSI guidelines and interpreted using 2023 CLSI breakpoints. CRE was defined by resistance to meropenem; CRPA was defined by resistance to meropenem and/or imipenem. Isolates with cefepime-taniborbactam MIC ≥16 µg/mL were characterized by whole genome sequencing. Isolates resistant to meropenem were screened for acquired β-lactamases by multiplex PCR/Sanger sequencing.

Results

In total, 97.1% of the 68 CRE isolates were inhibited by ≤16 µg/mL of cefepime-taniborbactam. The majority of CRE (51/68; 75.0%) produced a carbapenemase (40 KPC, 9 MBLs, 2 OXA-48) and 98.0% were inhibited by ≤16 µg/mL cefepime-taniborbactam, a substantially greater percentage than the most active comparator, meropenem-vaborbactam (82.4% susceptible). Cefepime-taniborbactam at ≤16 µg/mL inhibited 92.9% of all CRPA (n=308), 88.7% of meropenem-resistant P. aeruginosa (n=177), and 90.6% of carbapenemase-negative, meropenem-resistant P. aeruginosa (n=170) whereas the most active comparator, ceftazidime-avibactam, covered 84.7%, 75.7%, and 77.6% of these resistant subsets, respectively.

Conclusion

Cefepime-taniborbactam inhibited ≥94.1% of CRE isolates from the US, regardless of carbapenemase carriage. Similarly potent activity was observed for cefepime-taniborbactam against CRPA, including meropenem-resistant strains without a detected carbapenemase. The continued development of cefepime-taniborbactam appears warranted.

Disclosures

Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
137. Penicillin (PCN) Gradient Diffusion Overcalls Resistance and Promotes Unnecessary Vancomycin (VAN) Use in Enterococcus faecalis Bloodstream Infections (BSI)
Authors: Donohue Lindsay E , Cox Heather L , Thomas Jenni , Kidd Tiffany S , Mohammed Hiba N , Mathers Amy
Published: November 2023

Background

Reports of a PCN-resistant (R), ampicillin-susceptible (S) Enterococcus faecalis (PRASEF) phenotype associated with elevated piperacillin and imipenem minimum inhibitory concentrations (MICs) may drive hesitation to use these agents when a PCN MIC is unknown and/or result in the addition of a glycopeptide. However, PCN MICs by broth microdilution are not readily available in many clinical laboratories and some commercial methods may overcall PRASEF. We sought to assess the rate of overcalling PCN MICs by gradient diffusion compared to broth microdilution and the impact of PCN test requests and results on vancomycin (VAN) prescribing attributed to possible PRASEF BSI at a single academic medical center.

Methods

Retained clinical E. faecalis blood isolates with Etest® (BioMérieux, Inc.) PCN MICs collected from 2019 – 2022 were tested via automated broth microdilution (aBMD) plates (Sensititre™ Thermo Fisher Scientific, Inc.). MICs were interpreted according to CLSI breakpoints and compared for essential agreement (EA) and categorical agreement (CA) of Etest to aBMD. A retrospective chart review of all PCN-S or PRASEF BSI from 1/2021 – 12/2022 identified via antibiogram report generation (Theradoc® Premier, Inc.) plus all patients with a retained isolate was conducted to measure VAN days of therapy (DOT) attributed to concern for PRASEF.

Results

Of the 5 PCN-S and 19 PCN-R isolates via Etest MIC for which aBMD was performed, all tested PCN-S with an MIC50/90 of 4/8 mcg/mL. EA was 33% and CA was 21%, with a 79% major error rate (called resistant when susceptible). A total of 124 patient charts were reviewed (n=25 Etest PCN-R, n=99 Etest PCN-S). Total attributable VAN DOT was 102 across 19 patients (n=3 Etest PCN-R, n=16 Etest PCN-S), with a mean VAN DOT of 17 in PCN-R and 3 in PCN-S isolates.

Conclusion

False resistant PCN Etest MICs, as determined by aBMD comparison and consistent with published reports, fed concern regarding potential PRASEF emergence at our institution and led to unnecessary concomitant VAN in 15% of patients. Caution is advised when interpreting PCN susceptibility via this method. Inclusion of E. faecalis in the FDA indication for in vitro diagnostic use of benzylPCN Etest should be reconsidered.

Disclosures

Amy Mathers, MD, D(ABMM), Merck: Advisor/Consultant
2740. Letermovir for the Prevention and Treatment of Cytomegalovirus Infection in Solid Organ Transplant Recipients
Authors: Xhemali Xhilda , Urzen Courtney A , Blackmer Kristen A
Published: November 2023

Background

Cytomegalovirus (CMV) is a common infection that can lead to end-organ damage and graft rejection in solid organ transplant (SOT) recipients. Due to the increase in drug-resistant CMV and unfavorable side effect profile of available CMV-active agents, there is a need for additional prophylactic and treatment strategies in this patient population. The goal of this study is to evaluate SOT recipients prescribed letermovir for prophylaxis and/or treatment of CMV.

Methods

This study was a retrospective review of adult SOT recipients in the Cleveland Clinic Health System prescribed letermovir from 11/8/2017 to 8/1/2022. The primary objective was to describe the utilization of letermovir in SOT recipients. Secondary objectives included: proportion of SOT recipients that experienced CMV breakthrough on letermovir prophylaxis, proportion of SOT recipients that experienced refractory CMV infection on letermovir treatment, prevalence of letermovir resistance, and letermovir-induced adverse effects.

Results

A total of 45 patients were included in the study, with 52 letermovir courses. Lung was the most commonly transplanted organ (35%), followed by kidney (22%). 78% of patients were high-risk CMV and the most common immunosuppression regimen consisted of a calcineurin inhibitor in combination with a corticosteroid (82%). 11 patients received letermovir for primary CMV prophylaxis, with only one patient experiencing new/worsening viremia while on the agent. Of the 34 patients who received letermovir for secondary CMV prophylaxis, 11 experienced new/worsening viremia. 7 patients received letermovir for CMV treatment, at a median viral load of 991 IU/mL (IQR 603-2,738) on initiation and peak viral load of 3,892 IU/mL (IQR 1,407-10,209) while on therapy. No patients in the treatment group experienced refractory infection. 7/52 (13.5%) letermovir courses were discontinued due to new/worsening viremia, with no letermovir resistance identified. No letermovir-related adverse effects were documented.

Conclusion

Our study shows that letermovir appears to be effective in suppressing CMV viremia. Letermovir may be an alternative option for SOT recipients who are unable to tolerate or have resistance to traditional CMV therapeutics.

Disclosures

All Authors: No reported disclosures
2751. Cefiderocol Use in Treating Patients with Confirmed Stenotrophomonas maltophilia Infections in US Hospitals During January 2020 - June 2022
Authors: Cai Bin , Nguyen Sean T , Copeland Jennifer D , Song Hyun Jin , Slover Christine M
Published: November 2023

Background

Stenotrophomonas maltophilia (SM) infections have been associated with high mortality rates (21% to 69%), particularly in critically ill patients because of SM inherent resistance to many antibiotics, including carbapenems. This study describes cefiderocol (CFDC) treating hospitalized patients infected with SM in the US.

Methods

This retrospective observational study used January 2020-June 22 Premier Healthcare Database. Inclusion criteria are age ≥18 years, non-COVID, a positive SM culture without other Gram-negative pathogens identified within ±3 days and received CFDC ≥3 days on or after first SM culture. This study describes the patient characteristics, cefiderocol use pattern, and overall, 14-day and 28-day in-hospital all-cause mortalities (IHACM) with 95% confidence intervals (CI). First SM culture is the Index culture.

Results

Of 19 patients meeting the inclusion criteria, median age was 62 years with an interquartile range (IQR) of 56-76 years, 57.9% were male, 63.2% came from home, and 89.5% were admitted via emergency room or urgent care. Top comorbidities at admission were renal disease (68.4%), congestive heart failure (52.6%), chronic pulmonary disease (31.6%), and peripheral vascular disease (31.6%). Over 68% of patients were in the ICU, with the same rate of receiving both mechanical ventilation and vasopressor support at the time of index culture. Also 68.4% of index cultures were from respiratory and 10.5% from blood. CFDC was initiated ≤5 days of index culture in 8 (42.1%) patients, 6-20 days in 9 (47.4%) patients, and >20 days in 2 (10.5%) patients. Median days on CFDC was 8 days (IQR: 4-12), longer for patients who started CFDC later. All 19 patients received other antibiotics prior to CFDC. Twelve (63.2%) patients received other antibiotics during CFDC treatment, and the most common antibiotics were levofloxacin (50.0%), eravacycline (50.0%), cefepime (33.3%), or minocycline (33.3%). Median of hospital stays after index culture was 18 days (IRQ:8-30). Crude overall IHACM was 36.8% (95%CI: 15.8%-58.5%). Crude 28-day IHACM from index culture was 21.1% (95%CI: 2.7%-39.4%).

Conclusion

SM is a rare Gram-negative pathogen with limited treatment options. CFDC offers an additional treatment option against this pathogen. Further investigation is warranted.

Disclosures

Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Jennifer D. copeland, MS, Shionogi, Inc.: Employee (Medical/Micro) Christine M. Slover, PharmD, Shionogi,INC: Employee
2818. Investigating Urinalysis Criteria that Predict UTI: Impact of age, sex, and urine culture thresholds
Authors: Advani Sonali , North Rebecca M , Turner Nicholas A , Ahmadi Sahra , Denniss Julia , Francis Adero , Hasan Anum , Johnson Rachel M , Mirza Faryal , Pardue Sarah , Rao Meghana V , Rosshandler Yasmin , Tang Helen , Schmader Kenneth E , Anderson Deverick J
Published: November 2023

Background

Urinalysis (UA) results are used by clinicians and laboratories to aid in the diagnosis of UTI. However, optimal UA parameters have not been systematically investigated or validated for different populations. Our objectives were to assess the performance of UA in predicting UTI and to stratify UA performance by age, sex, and culture thresholds.

Methods

We conducted a retrospective cohort study of adult non-catheterized inpatient and ED encounters with paired UA and urine cultures (24 hours apart) from 5 community and academic hospitals in three states (NC, VA, GA) between 01/01/2017 and 12/31/2019. Trained abstractors collected clinical and demographic data for a random sample of patients. Patients were classified as having UTI, asymptomatic bacteriuria or ‘not UTI’ based on IDSA guidelines using signs/symptoms and microbiology data. We evaluated the performance of relevant UA parameters in predicting UTI by assessing sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria (Figure 1) and used area under receiver operating curves (AUROC) to identify the 5 best-performing models, and stratified results by age, sex, and lower urine culture bacterial threshold (1000 colony forming units).

Results

Of 219,338 encounters, 3392 charts were included and reviewed; 723 (21.3%) patients met criteria for UTI. Females and older adults had a higher incidence of UTIs and ASB (P< 0.05; Table 1). Absence of pyuria (or leukocyte esterase) had a high NPV for UTI (Table 2). Combined UA parameters performed better than pyuria alone with regards to NPV and AUROC, specifically models 1 and 5 (Table 3). UA parameters used in these models performed differently based on age, sex and urine culture thresholds, with limited utility in older women and UTIs with lower bacterial threshold (Table 4).

Conclusion

Our review of laboratory and symptom data from a diverse population dataset revealed that combined UA parameters were better at predicting UTI, but performance of UA parameters differs based on age, sex, and urine culture thresholds. Our approach highlights the need to move away from a one-size fits all approach to using population specific UA cut-offs for patients with UTI symptoms.

Disclosures

Sonali Advani, MBBS, MPH, FIDSA, bioMérieux: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant Nicholas A. Turner, MD, MHSc, PDI: Research contract to assess efficacy of cleaning agent
668. The clinical effectiveness of Fidaxomicin compared to Vancomycin in the treatment of Clostridioides difficile infection in immunocompromised hosts, a single center study
Authors: Alsoubani Majd , Chow Jennifer K , Rodday Angie Mae , Kent David , Snydman David R
Published: November 2023

Background

Patients with immunocompromising conditions are at increased risk of C.difficile infection (CDI) and recurrence. Fidaxomicin reduces the risk of recurrence in immunocompetent hosts. However, there is limited data on fidaxomicin effectiveness in hosts with immunocompromising conditions.

Methods

We retrospectively assessed the treatment of CDI among patients with immunocompromising conditions who were diagnosed between 2011 and 2021 at Tufts Medical Center. Patients were considered to be treated by fidaxomicin or vancomycin if they received ≥72 hours of the agent. Patients less than 18 years, those who did not receive treatment for CDI, and those treated with metronidazole only were excluded. The study outcome was a composite of failure to achieve clinical cure within 72 hours of treatment initiation, relapse within 30 days following completion of initial treatment and death due to CDI. Time to event analysis used a cause specific Cox proportional hazards to compare the rate of the composite outcome in the two groups, accounting for the competing risk of death from other causes. Multiple imputation was used for missing variables but not the outcome.

Results

A total of 238 patients with immunocompromising conditions received vancomycin (n= 38) or fidaxomicin (n= 200) for treatment of CDI. Patients who received vancomycin were significantly more likely to be male (51.5% vs 26.2%, p 0.005) and to have had community acquired infection (31.1% vs 9.5%, p 0.03) compared to fidaxomicin (Table 1). The composite outcome occurred in 48 (24%) patients in the vancomycin group compared to 5 (13.2%) in the fidaxomicin group. In the multivariable model adjusted for sex, number of antecedent antibiotics, antibiotics during treatment, severity and type of immunosuppression, fidaxomicin was associated with 65% reduction in the hazard of the composite outcome compared with vancomycin (HR 0.35, 95% CI 0.12-0.99) (Table 2).

Conclusion

The use of fidaxomicin was more effective than vancomycin in preventing poor CDI outcomes among patients with immunocompromising conditions. The study may have residual confounding by indication and limited generalizability based on a single site. Future studies should confirm our findings.

Disclosures

Jennifer K. Chow, MD, MS, Kamada: Grant/Research Support|Merck: Grant/Research Support|Moderna: DSMB David Kent, MD, W.L. Gore: Grant/Research Support David R. Snydman, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres therapeutics: Advisor/Consultant|Seres Therapeutics: Grant/Research Support|Summit Therapeutics: Grant/Research Support