bluuebunny/crossref_metadata_2025_split huggingface dataset:
579. Clinical and Drug Resistance Characteristics of Providencia spp. Infections
Authors: Kale-Pradhan Pramodini , Lim Lauren , Graskewicz Heather , Malviya Meenal , COYLE M E R E D I T H M , Giuliano Christopher , Johnson Leonard B 
Published: November 2023

Abstract

Background
Providencia is a gram-negative bacillus that colonizes the urinary tract and is often resistant to many antimicrobials. This study aimed to evaluate resistance patterns of Providencia spp (P. spp) and clinical outcomes due to the paucity of topical data.

Methods
A multi-center, descriptive, retrospective chart review of adult patients with P. spp. infections was conducted from January 1, 2020 to May 31, 2022. The primary outcome was to describe the drug resistance patterns of P. spp. isolates. The study’s secondary outcome was to evaluate the clinical outcomes of patients with P. spp infections.

Results
Of 312 patients screened, 243 were excluded primarily for polymicrobial infections. The mean age was 70 years and 39 (56.5%) were males. Of the 69 included cases, 46 (66.7%) were P. stuartii, 21 (30.4%) P. rettgerri, and 2 (2.9%) P. alcalifaciens. The most common infections were bacteremia 38 (55.1%), with urinary and wound being the most frequent bacteremia source; followed by 28 (40.6%) urinary tract and 3 (4.3%) wound infections. 45 patients (65.2%) had urinary catheters. Primary antibiotics used for treatment consisted of ceftriaxone, 25 (36.2%), cefepime, 20 (29%), and meropenem, 10 (14.5%). Five of 69 (7.2%) cases were multidrug resistant and required meropenem. Nineteen patients (27.1%) died during their admission but none related to Providencia infections. Ten of the 69 patients (14.5%) were readmitted within 30 days for reasons unrelated to progression or recurrence of Providencia infections.

Conclusion
Providencia bacteremia was the most common infection. Third generation cephalosporins remain an appropriate choice of antibiotics for P. spp. However, P. stuartii was the only species with multidrug resistance. Future studies should be carried out to confirm this observation.

Disclosures
All Authors: No reported disclosures
642. The impact of novel E1:M407I mutation on replicative fitness of the Chikungunya virus ECSA-IOL strain during infection of mammalian and mosquito cells,
Authors: Khan Bilal A , Ullah Saif , Khan Saeed 
Published: November 2023

Abstract

Background
Chikungunya virus (CHIKV) is an Alpha virus which is transmitted by Aedes genus of mosquitoes. It causes febrile illness with severe arthralgia, myalgia and rashes. Since 2000, the re-emergence of this pathogen have made it a global health security threat as it has caused severe form of diseases with epidemics of large magnitude and also spread to European and American continent. Studies have identified different point mutations in E1 and E2 region associated with virulence and infectivity, which is behind these severe epidemics. Pakistan reported first CHIKV outbreak with more than 30,000 infections from its largest city in 2016 which is already endemic for Dengue virus (DENV).

Methods
32 CHIKV PCR-positive serum samples were collected from molecular pathology section of DUHS followed by RNA extraction and amplifcation of E1 region by PCR. The amplified products were prurified and sanger sequenced by BigDye termination method. Mutation analyses & Bayesian phylogeny was done by bioinformatic tools. CHIKV E1:M407I mutation was cloned in to CHIKV wild type infectious cDNA clone plasmid (SL-CK-1) by site directed mutagenesis (SDS). In vitro viral RNA was synthesized after plasmid linearization, which was electroporated into VERO-CCL-81 cells. M407I mutant virus was recovered from the culture, titrated by plaque assay and sanger sequenced to confirmed the M407I mutation. Viral competition assay was performed in mammalian and mosquitoes cell lines to determine the relative replicative fitness of mutant CHIKV virus over wild type.

Results
Sequence analysis revealed 7 unique mutations in E1 including one mutation (M407I) in more than half of the sequenced samples. Phylogenetic analyses revealed this outbreak was caused by CHIKV-IOL genotype with possible inception from India. Virus competition assay showed relative replicative fitness for CHIKV E1:M407I mutant in Vero-CLL-81 and AAG2 cells have greater advantage while in C6/36, it has slight advantage over wild type virus.

Conclusion
This study reports a novel mutations in E1 protein of CHIKV with fitness advantage over wild type strain. Phylogeny revealed the outbreak was caused by A226-IOL strain with possible origin from ancestral strain of Indian outbreak.

Disclosures
All Authors: No reported disclosures
919. Household Flu Transmission and Healthcare Resource Use among Patients Treated with Baloxavir versus Oseltamivir for Influenza: An Outpatient Prospective Survey in the United States
Authors: Best Jennie H , Sadeghi Mitra H , Sun Xiaowu , Seetasith Arpamas H , Albensi Lisa , Joshi Seema , Zervos Marcus 
Published: November 2023

Abstract

Background
Influenza is a common seasonal infectious disease that has broad medical, economic, and social consequences. Understanding how flu antiviral use affects transmission to household (HH) members is critical to inform clinical practice. Objectives of this study were to compare the incidence of HH transmission (primary) and healthcare resource utilization (HRU, secondary) in influenza patients treated with baloxavir (BALOX) compared with oseltamivir (OSELT). This is the first analysis to examine the effectiveness of BALOX vs OSELT for reducing transmission in a real-world setting in the US.

Methods
Patients were recruited from October 2022 to March 2023 via CVS Pharmacy in the US. Patients were eligible for inclusion if: ≥ 18 years, filled an Rx for BALOX or OSELT ("index" day) ≤ 2 days from flu symptom onset and also reported taking the therapy, had no HH flu ≤ 7 days pre-index, had no COVID ≤ 30 days pre-index, and had ≥ 2 persons in HH. Patients were contacted via email or call center from Days 4 though 8 post-index to inform and/or remind patients about the online survey. Patients completed the survey on Days 6, 7, or 8 post-index. BALOX-treated patients were matched (non-randomized) with up to 3 OSELT-treated patients on same RX fill date. Household transmission (reported by index patient) and all-cause HRU (of the index patient) in the 8 days post-index were assessed using chi-square and Fisher's exact tests.

Results
Of 77,314 unique patients contacted, 1,301 (1.7%) patients consented. Of 356 eligible patients, 275 (89 BALOX-treated and 186 OSELT-treated patients) completed the survey and were included in the analysis. Patients were mean age 45, female (65%), and White (87%). Lower HH transmission was observed with BALOX compared with OSELT therapy (18.0% vs 27.4%; standardized mean difference = 0.23; RR = 0.66; p= 0.09; Figure 1). HRU was also numerically lower in the BALOX-treated group, particularly emergency department visits (0.0% vs 4.3%; p = 0.06; Table 1); no hospitalizations were reported.
Proportion of patients with healthcare resource utilization

Conclusion
The findings in this real-world study suggest that treatment of influenza with BALOX may decrease transmission to household members and reduce healthcare resource utilization compared with OSELT treatment. Future research could validate these findings in larger populations.

Disclosures
Jennie H. Best, PhD, Genentech: Stocks/Bonds Mitra H. Sadeghi, PharmD, Genentech, Inc.: Stocks/Bonds Xiaowu Sun, PhD, CVS: Stocks/Bonds Arpamas H. Seetasith, PhD, Genentech, Inc.: Stocks/Bonds Marcus Zervos, MD, Contrafect: Advisor/Consultant|GSK: Grant/Research Support|Johnson and Johnson: Grant/Research Support|Pfizer: Grant/Research Support
1144. Dissociative Neurological Symptom Reactions Following COVID-19 Vaccination in Adolescents in Japan
Authors: Horikoshi Yuho , Yamanaka Takayuki , Aizawa Yuta , Nakamura Yukitsugu , Shoji Takayo , Okumura Toshihiko , Cho Yoshiaki 
Published: November 2023

Abstract

Background
In 2019, the WHO categorized immunization stress-related reactions as an adverse event following immunization (AEFI). Understanding AEFI is essential for determining an appropriate communication strategy to sustain trust in vaccination. Delayed response to immunization includes dissociative neurological symptom reactions (DNSRs), which are characterized by functional neurological symptoms. DNSRs following immunizations are quite rare, but it is often wrongly linked to causal relationship with vaccines that the public might perceive unnecessary fear. As DNSRs following vaccination in adolescents are currently understudied, the present report aimed to describe the clinical features of DNSRs following COVID-19 vaccination.

Methods
The multicentric study was conducted between July 2021 and March 2023 at seven tertiary pediatric medical centers accepting patients with persistent AEFI. Patients aged 18 years or younger were included. Their charts were reviewed retrospectively for demographic data, symptoms, and the outcomes of DNSRs following COVID-19 vaccination.

Results
In total, 46 patients aged 6 to 17 years were referred for persistent AEFI following COVID-19 vaccination. Among these, eight received the diagnosis of DNSR. Female patients comprised 87% of the cohort. All the patients had received the Comirnaty vaccine (Pfizer). Before DNSR onset, seven and one patient had received their first and second dose of Comirnaty, respectively. Two and one of the eight patients had a mental handicap and autism spectrum disorder, respectively. The DNSR symptoms included weakness (37%), gait irregularity (25%), speech difficulty (25%), paralysis (12%), and non-epileptic seizure (12%). The duration from vaccination to symptom onset ranged from 0 to 14 days (median: 1 day; IQR: 1-2 days). Symptom duration was 0.5-11 months (median: 5 months; IQR: 1-7 months). The outcomes included resolution (25%), improvement (62%) and no change (12%).
Patients with DNSR symptoms
This is summary of patients presenting with DNSRs.

Conclusion
DNSRs following COVID-19 vaccination were observed predominately in female, adolescent patients and had a favorable, long-term outcome.

Disclosures
Yuho Horikoshi, MD, Shionogi Pharm: Grant/Research Support
1149. Contribution of S.pneumoniae Serotypes in Adults with Invasive Pneumococcal Disease (IPD) and Pneumococcal Community-acquired Pneumonia (pCAP)
Authors: Apodaca Kevin , Grant Lindsay , Yan Qi , Theilacker Christian , Ali Mohammad , Pride Michael W , Gessner Bradford D , Jodar Luis 
Published: November 2023

Abstract

Background
Invasive pneumococcal disease (IPD) serotype distribution has been used to infer the serotype distribution of pneumococcal community acquired pneumonia (pCAP) in countries where only IPD data exist. However, serotype distribution of IPD and pCAP may differ. We sought to identify differences in contribution of serotypes causing pCAP versus IPD.

Methods
Eligible countries had serotype data available from adults for both IPD (determined by standard serotyping methods of cultured isolates) and pCAP (determined by serotype-specific urinary antigen detection (UAD) assays or culture for at least three years following PCV13 introduction into the pediatric national immunization program (NIP). Analyses were restricted to serotypes included in UAD assays. We further restricted analysis to serotypes not in PCV13 but detected by UAD assays (serotypes 2, 8, 9N, 10A, 11A, 12F, 15B/C, 17F, 20, 22F, and 33F), because PCV13 introduction into the NIPs has led to vaccine serotype disease reduction. The total positive of these serotypes was the denominator in the serotype-specific proportion calculations for both IPD and pCAP

Results
We included seven countries. IPD serotype as well as pCAP distribution varied substantially across countries, while within countries, IPD and pCAP serotype distribution varied modestly (Figure1, Table 1) For the three most common pCAP serotypes across the seven countries, the absolute differences in the percent due to pCAP across countries were 19% (serotype 8), 10% (serotype 22F) and 10% (serotype 11A). For the same three serotypes, respectively, the absolute differences in the percent due to IPD across countries were 47%, 18%, and 17%. For these same three serotypes, the absolute differences in the percent due to pCAP vs, IPD within a country ranged from 1% to 14%, 1% to 6%, and 2% to 11%.

Conclusion
pCAP and IPD serotype distribution were relatively aligned within countries. By contrast IPD and pCAP serotype distribution varied substantially across countries. Consequently, while the most accurate data for country-specific pneumococcal vaccine decision-making will come from combined IPD and CAP studies, countries without CAP data should rely on local IPD serotype distribution rather than CAP data from other countries.

Disclosures
Kevin Apodaca, MPH, Pfizer Inc.: Stocks/Bonds Lindsay Grant, PhD, MPH, Pfizer Inc.: Stocks/Bonds Qi Yan, PhD, MS, Pfizer Inc: Stocks/Bonds Christian Theilacker, MD, DTM&H, Pfizer Inc: Stocks/Bonds Mohammad Ali, PhD, Pfizer Inc: Stocks/Bonds Michael W. Pride, PhD, Pfizer: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer Inc: Stocks/Bonds
Possible Worlds as Propositions
Authors: Deasy Daniel 
Published: November 2023

Abstract
Realists about possible worlds typically identify possible worlds with abstract objects, such as propositions or properties. However, they face a significant objection due to Lewis (1986), to the effect that there is no way to explain how possible worlds-as-abstract objects represent possibilities. In this paper, I describe a response to this objection on behalf of realists. The response is to identify possible worlds with propositions, but to deny that propositions are abstract objects, or indeed objects at all. Instead, I argue that realists should follow Prior (1971) and others in treating higher-order quantification (e.g. quantification into predicate or sentence position) as a genuine form of quantification in its own right, and so in particular, not to be analysed in terms of first-order quantification over abstract objects. I argue that from this ‘higher-orderist’ perspective, there is a relatively straightforward answer to the question of how possible worlds-as-propositions succeed in representing possibilities.
Real-world efficacy of belimumab in systemic lupus erythematosus: a prospective cohort from a single centre in China
Authors: Zhao Yin , Qi Fumin , Bai Jinyu , Zhang Na , Yang Tong , Sun Wenwen , Li Xin , Wei Wei 
Published: November 2023

Abstract

Objective
The objective of this study was to explore the efficacy and safety of belimumab among Chinese patients with SLE in a real-world setting.

Methods
A prospective cohort study was performed, and SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were consecutively enrolled from July 2021 to December 2022. Based on baseline characteristics, the patients were divided into three groups: the newly diagnosed group, the relapsed group and the refractory group. Patients in the newly diagnosed group were newly diagnosed with SLE within 4 weeks of starting belimumab. Patients in the relapse group had experienced a severe flare. Refractory patients were patients with unsatisfactory GC taper and/or disease activity control. Clinical data were collected, and disease assessments were conducted regularly. Newly diagnosed patients with SoC alone and healthy controls (HCs) were also enrolled.

Results
A total of 123 SLE patients were included in the analysis, with a median follow-up period of 12 months (range 3–18 months). Thirty-three out of 123 patients were newly diagnosed, 32 had relapsed disease, and 58 had refractory disease. The SLE Responder Index 4 (SRI-4) response was achieved with good tolerance by 55.77% of patients at 3 months, 56.63% at 6 months, 63.24% at 9 months, 63.64% at 12 months and 57.14% at 18 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall and in each group. Of the three groups, the newly diagnosed group had the highest SRI-4 rate as well as the greatest improvement in serological parameters and SLEDAI-2K. Compared with newly diagnosed patients with SoC alone, the cumulative prednisone intake of newly diagnosed patients taking belimumab was significantly decreased.

Conclusion
Our data supported the efficacy of belimumab in Chinese SLE patients in a real-life setting. Our study also provided new evidence indicating remarkable achievement of the SRI-4 response during belimumab therapy in newly diagnosed SLE patients.
Closing-wedge Osteotomies: Can We Do and Teach Better?
Authors: Weltsch Daniel , Juels Michaela , Chen Kevin Yining , Talathi Nakul , Silva Mauricio , Thompson Rachel M. 
Published: November 2023

Background:
Wedge osteotomies are ubiquitous in pediatric orthopaedics and limb deformity surgery; however, there is no universally preferred methodology for these procedures. This study aims to determine the relative accuracy and effectiveness of several measuring and marking methods to guide best practices for wedge-shaped osteotomies in long bones.

Methods:
An observational cohort study was completed. Orthopaedic residents (postgraduate years 1 to 5) completed 30-degree wedge osteotomies on a sawbone (Pacific Research Lab) femur utilizing a standard oscillating saw under 3 measuring conditions: (1) no measurement tool, (2) 30-degree triangle, and (3) goniometer, in combination with 2 different marking methods: (1) marking pen or (2) pin placement. Demographic characteristics and osteotomy performance (quality, completion time, and accuracy) were assessed. Quality was ranked as perfect (1), mild step-off (2), or gross surface irregularity (3). Multivariate regressions and analysis of variance were performed comparing demographics, osteotomy performance, and measuring methods.

Results:
Twenty-four residents were included for analysis; 6 were female (25%). Female sex was independently associated with longer completion time when evaluating all combined scenarios (138 vs. 99 s, P=0.003) without differences in surface quality or angle accuracy. There were no significant associations between measuring technique and accuracy or surface quality, but use of the goniometer and the triangle both were associated with significantly longer completion time compared with no visual aid (P=0.002 and 0.007). When controlling for measuring technique, use of the pen as a marking technique had significantly shorter completion times (P<0.001), higher surface quality (P<0.001), and better accuracy (P<0.001) than guide pins.

Conclusions:
We recommend the use of a marking pen in combination with the surgeon’s preferred measuring guide to optimize trainees’ performance of closing wedge osteotomies. Future research is necessary to corroborate these findings in a higher fidelity setting, such as a cadaveric study. Further, while male residents complete wedge osteotomies quicker than female residents, quality and accuracy are comparable among trainees. Slower pace should not be conflated with poor performance but rather should inform effective intraoperative teaching for diverse trainees.
Efficacy and safety of clarithromycin for patients with sepsis or septic shock: a systematic review and meta-analysis
Authors: Zhao Pengyue , Yao Renqi , Yang Jiaqi , Wen Wei , Yao Yongming , Du Xiaohui 
Published: November 2023

Abstract

Background
Clarithromycin exerts an immunomodulatory role in several human diseases. However, whether this effect improves the prognosis in patients with sepsis remains controversial, and higher levels of clinical evidence are urgently needed. To the best of our knowledge, no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in sepsis.

Methods
A comprehensive literature search of PubMed, EMBASE, and the Cochrane Library was conducted up to December 31, 2022. Only randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were included. Data were pooled by applying a fixed-effects model and a relative risk (RR) estimate with 95% confidence intervals (CIs) using Review Manager (version 5.3; Cochrane Collaboration, Copenhagen, Denmark).

Results
Three randomized controlled trials involving a total of 910 patients were included. The pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome (RR: 1.51; 95% CI: 1.02–2.25; P = 0.04; I
2 = 0%), 28-day mortality (RR: 1.09; 95% CI: 0.87–1.36; P = 0.46; I
2 = 0%), and 90-day mortality (RR: 0.86; 95% CI: 0.71–1.03; P = 0.10; I
2 = 81%) in patients with sepsis or septic shock. Moreover, there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group (RR: 1.02; 95% CI: 0.87–1.19; P = 0.83; I
2 = 18%).

Conclusion
Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with clarithromycin. However, administration of clarithromycin did not increase the risk of adverse events.
A Novel Framework for Optimizing Efficiency and Education in Microsurgical Breast Reconstruction
Authors: Lester Mary E. , Berns Jessica , Dawson Steven , Newsom Keeley , Hartman Brett , Hassanein Aladdin H. 
Published: November 2023

Summary:
Deep inferior epigastric perforator (DIEP) flaps are becoming the most frequent choice for autologous breast reconstruction. There are many benefits to DIEP flaps, but the procedures can be lengthy and have a steep learning curve. The balance of efficiency and education can be difficult to achieve. A framework was implemented to focus on both efficiency and education at each stage of the DIEP flap procedure. The author’s methods to improve efficiency include a two-team approach with assigned roles for faculty and residents. The roles are consistent across the institution. Methods to enhance education include practice in a laboratory-based microsurgical training course and assigning goals for the rotation. Trainees include independent and integrated plastic surgery residents without microsurgical fellows. Bilateral DIEPs are performed with two attendings, and unilateral DIEPs, with one attending. A retrospective review identified patients undergoing DIEP flap reconstruction from 2017 to 2020. Outcome measures include operative time and complications, which are comparable to previously published data. Focusing on education allows residents to learn each stage of the case. The authors present a framework for training residents in DIEP flap reconstruction to optimize efficiency and education.