bluuebunny/crossref_metadata_2025_split huggingface dataset:
890. Bundled Antimicrobial Stewardship Intervention Reduces Inpatient Third Generation Cephalosporin Use without Restriction
Authors: Hopkins Teri L , Yang Linda , Douglass Dana , Sanchez Chelsea , Morneau Kathleen , Cadena-Zuluaga Jose , Walter Elizabeth 
Published: December 2022

Abstract

Background
The use of third generation cephalosporins (3GC) has been linked to collateral damage such as increased risk of infection with C. difficile, ESBL-producing organisms, VRE, and MRSA. Reduction in use of 3GC has been shown to reduce prevalence of these infections, particularly with C. difficile and ESBLs. An increase in 3GC use was observed at our facility in 2019 and 2020, likely due to targeted fluoroquinolone reduction initiatives in 2019 and COVID-19 surges in 2020. A multifaceted intervention targeting 3GC reduction without restriction was implemented starting in December 2020. Figure 1Monthly third generation cephalosporin use (Days of Therapy per 1000 patient days) from January 2019 to December 2021.

Methods
We conducted a retrospective quasi-experimental study evaluating the impact of a combination of interventions intended to reduce 3GC use. The intervention included modification of local clinical guidelines for urinary tract infection (UTI) and community acquired pneumonia (CAP), provider education, and daily review of active 3GC orders in 2021. Local guideline changes include preferred use of ampicillin/sulbactam and amoxicillin/clavulanate for CAP and cefazolin and cephalexin for UTI over 3GCs. Use of first generation cephalosporins for UTI was supported by local antibiogram susceptibilities for common UTI pathogens. Days of therapy (DOT) per 1000 patient days were collected monthly and yearly for ceftriaxone, ceftazidime, cefpodoxime, and cefdinir for pre-intervention (January 2019 to December 2019 and January to December 2020) and post-intervention (January 2021 to December 2021) periods.

Results
3GC use significantly decreased from 89.52 DOT per 1000 patient days in 2020 to 53.06 in 2021, a 40.73% reduction. To account for increases in antibiotic use during COVID-19 surges in 2020 as a potential confounding variable, 2019 3GC use was also compared to 2021 use. A 31.40% decrease was seen, with 77.35 DOT per 1000 patient days in 2019. This effect was sustained through COVID-19 surges in January and August 2021 (Figure 1).

Conclusion
A combination of interventions without restriction of 3GC was successful in reducing inpatient use of this class of antibiotics, including through two COVID-19 surges in 2021. Further study is required to determine impact on clinical outcomes, such as C. difficile and antimicrobial resistance rates.

Disclosures
All Authors: No reported disclosures.
909. Impact of Implementing an IV to PO Antibiotic Treatment Protocol for Orthopedic Infections on Prescribing Habits and Health Utilization Outcomes
Authors: Gallagher Chanah , Benefield Russell J , Certain Laura 
Published: December 2022

Abstract

Background
The Oral versus Intravenous Antibiotics for Bone and Joint Infection Trial concluded that oral antibiotics administered during the first six weeks of therapy for orthopedic infections were non-inferior to parenteral antibiotics. Previously, we also conducted a retrospective cohort study of patients at our center with an orthopedic infection. Patients transitioned to oral therapy had significantly fewer adverse events and similar incidences of one year treatment failure compared to patients maintained on parenteral vancomycin.

Methods
To increase use of oral antibiotics for orthopedic infections, we created a protocol for changing IV to PO antibiotics prior to hospital discharge. We evaluated its effect on prescribing practices and healthcare utilization outcomes. Patients with an orthopedic infection were included if they were discharged within the 90-day pre- and post-protocol study periods, had an inpatient Infectious Disease consult, and were initiated on parenteral vancomycin while inpatient. The primary outcome compared the incidence of oral antibiotics prescribed at discharge. Secondary outcomes included incidence of adverse drug reactions, discharge dispositions, hospital length of stay, canceled follow-up appointments, unplanned readmissions, and early treatment failure.

Results
Fifty patients were included, 22 and 28 patients in the pre- and post-protocol groups, respectively. Twenty-three (82%) patients in the post-protocol group were prescribed oral antibiotics at discharge compared to 8 (36%) patients in the pre-protocol group. Twenty-three (82%) patients in the post-protocol group were discharged home compared to 13 (59%) patients in the pre-protocol group. Of note, 7 (25%) patients in the post-protocol group had early treatment failure compared to 1 (5%) patient in the pre-protocol group, and 8 (29%) patients in the post-protocol group compared to 4 (18%) patients in the pre-protocol group had an unplanned readmission.

Conclusion
Providing physicians with an oral antibiotic protocol for orthopedic infections significantly increased the number of oral antibiotic prescriptions at hospital discharge, but the higher rates of treatment failure observed after protocol implementation are concerning and warrant further investigation.

Disclosures
Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support.
946. Establishing Antimicrobial Stewardship Programme at Four Secondary Care Hospitals in India through Hub and Spoke Model with Christian Medical College, Vellore as Guiding Centre
Authors: Kumar Prasanna , Rupali Priscilla 
Published: December 2022

Abstract

Background
The high burden of antimicrobial resistance in India necessitates an urgent implementation of Antimicrobial Stewardship programs (ASP). Most ASP are based at tertiary care centres, with sparse data available regarding the effectiveness of an ASP in a low resource primary/secondary care setting.

Methods
We adopted a hub and spoke model to implement ASP in these low resource settings. The study consisted of three phases. Initial phase captured baseline antimicrobial days of therapy DOTs data with no feedback, followed by intervention phase wherein a few chosen interventions were implemented. Physicians of four chosen hospitals were trained via a blended customized distance education training programme, assisted with development of antibiogram based on their local hospital microbial resistance patterns via WHONET, followed by development of hospital specific antibiotic policy and augmentation of the existing laboratory skills by training personnel at the central facility. This was followed by a post intervention phase with a prospective review and feedback by trained personnel with assessment of DOTs.

Results
During the baseline phase, 1459 patients from all four sites were enrolled; 1233 patients were enrolled in the intervention phase. Both groups had comparable baseline characteristics. The key outcome, DOT per 1,000 patient days, was 1952.63 in the baseline phase. The DOT/1000 patient days was significantly lower in the post intervention period, at 1483.06 (P =0.001). Quinolones, Macrolides, Cephalosporins, Clindamycin, and Nitroimidazole use significantly decreased in the post intervention phase. Rate of de-escalation was significantly higher in the intervention phase compared to the baseline phase (44% vs 12.5%; P &lt; .0001), suggesting a definite trend with regard to the judicious use of antibiotics. Post intervention phase revealed that 79.9% of antibiotic use was justified. Overall, the recommendations given by the ASP team were fully followed in 946 cases (77.7%), partially followed in 59 cases (4.8%), and not followed in 137 cases (35.7%). No adverse events were noted.

Conclusion
Our Hub and Spoke model of ASP was successful in implementing ASP in secondary care hospitals in India which is the need of the hour.

Disclosures
Priscilla Rupali, MD, DTM&H, PFIZER: Grant/Research Support|PFIZER: Grant/Research Support.
1123. EDP-235, A Potent and Once-daily Oral Antiviral, Demonstrates Excellent Penetration into Macrophages and Monocytes, with the Potential for Mitigation of Cytokine Storm in High-Risk COVID-19 Patients
Authors: Li Yang , Zang Tianzhu Indy , Xu Lisha , Leonard Daniel , Hoang Khanh , Greizer Tim , Zhang Shucha , Foster Caroline , Huang Meng , Kibel Jonathan , Klaene Joshua , Or Yat Sun , Jiang Li-Juan 
Published: December 2022

Abstract

Background
Macrophages, including lung alveolar macrophages (AM), and monocytes are the first lines of defense against SARS-CoV-2. Several reports have suggested that SARS-CoV-2 can hijack AM and monocytes for replication and viral spread, which may, in turn, drive the cytokine storm associated with severe COVID-19. Herein, we describe one of many advantageous features that EDP-235, a novel and potent SARS-CoV-2 3C-like protease (3CLpro) inhibitor under development as a once-daily oral antiviral therapy for COVID-19, displays - excellent penetration into macrophages and monocytes.

Methods
Intracellular uptake of EDP-235 was tested side-by-side with nirmatrelvir in rat lung AM, human monocytes and human macrophages. To determine the in vivo drug distribution into lung AM, rats were dosed orally with 25 mg/kg of EDP-235 or nirmatrelvir and plasma and AM drug levels were analyzed by LC/MS/MS.

Results
The ratios of intracellular to extracellular concentrations of EDP-235 in rat lung AM, human monocytes and human macrophages were 22.8, 22.7 and 30.5, respectively. In contrast, nirmatrelvir had ratios of 1.2 to 1.5 in these cells. Consistent with the in vitro observations, EDP-235 showed favorable rat AM penetration with an AUC0-24 ratio of 28.4 (AM over plasma), and nirmatrelvir had much less rat AM penetration with an AUC0-24 ratio of 0.5 (AM over plasma). EDP-235 had respective AUC0-24 values of 9.6 and 271.9 h·μg/mL in rat plasma and AM, while the AUC0-24 values of nirmatrelvir in rat plasma and AM were 2.7 and 1.2 h·μg/mL, respectively.

Conclusion
EDP-235, a novel and potent SARS-CoV-2 3CL protease inhibitor, demonstrated excellent penetration into monocytes and macrophages, including lung AM. EDP-235 has the potential to eliminate the viral replication of SARS-CoV-2 in these critical immune cells, thus mitigating macrophage-mediated cytokine storm in high-risk COVID-19 patients. Clinical trials with EDP-235 for COVID-19 treatment and prevention are ongoing.

Disclosures
All Authors: No reported disclosures.
Introduction
Authors: Panaccio Claude 
Published: December 2022

Abstract
The Introduction spells out the aim and scope of the book. It explains in what sense this work is an “introduction” to William of Ockham’s nominalism and that it stresses the philosophical interest of this medieval approach in the context of today’s philosophical debates. It briefly outlines the three central theses of Ockham’s nominalism, touching on the notion of singularity of things, the notion of relations, and the concept of quantities. Ockham’s influence on later thinkers, as well as the context in which he produced his works, are outlined. The Introduction also provides a short biography of Ockham.
Epistemology
Authors: Panaccio Claude 
Published: December 2022

Abstract
Chapter 5 explains how human knowledge is possible according to Ockham in a world exclusively made up of individuals. For this, it first describes Ockham’s theory of cognitive acts: intuitive cognitions, abstractive cognitions, connotative conceptual acts (including basic relational concepts), and judgements. The chapter then introduces Ockham’s theory of mental language as endowed with a grammar and composed both of concepts that are naturally acquired and of innate syncategorematic terms (conjunctions, quantifiers, prepositions, etc.). It shows, finally, how this mental apparatus gives rise to evident cognition, to knowledge of both contingent and necessary propositions through demonstrations and inductive reasonings, and to the construction of scientific disciplines.
Mary Shepherd
Authors: Boyle Deborah 
Published: December 2022

Abstract
This guide leads readers systematically through the arguments of Mary Shepherd’s two books. Chapters 1–4 cover the arguments in the Essay upon the Relation of Cause and Effect (1824), where Shepherd argues that causal principles can be known by reason to be necessary truths and that causal inferences can be rationally justified. Shepherd’s primary target in this work is Hume, but she also addresses the views of Thomas Brown and William Lawrence. Shepherd considered her second book, Essays on the Perception of an External Universe, and Other Subjects Connected with the Doctrine of Causation (1827), to be an extension of the earlier project on causation; here, she appeals to the causal principles established in the first book to argue that we can know through reason that an external world of continually existing objects must exist independently of us, as the causes of our sensations. Chapter 5 of this Guide addresses Shepherd’s accounts of sensation and reasoning; Chapters 6–9 lead the reader through the arguments of the Essays, as well as laying out Shepherd’s views on skepticism and Berkeleyan idealism, her accounts of mind and body, her philosophy of religion, and the solutions she offers to two puzzles about vision.
Shepherd’s Life and Context
Authors: Boyle Deborah 
Published: December 2022

Abstract
This chapter provides a biographical sketch of Mary Shepherd, as well as an overview of the contents of her two books. In An Essay upon the Relation of Cause and Effect (1824), Shepherd argues that causal principles can be known by reason to be necessary truths. In Essays on the Perception of an External Universe, and Other Subjects Connected with the Doctrine of Causation (1827), Shepherd extends the earlier project, arguing that through our knowledge of causation, we can also know through reason that an external world of continually existing objects must exist independently of us. This chapter also provides a survey of the philosophical landscape in which Shepherd was working, including the Scottish common sense philosophy of Thomas Reid, Dugald Stewart, and Thomas Brown; Berkeleyan idealism; the French “ideologues”; and British moral theorists. The chapter ends with a brief account of the reception of Shepherd’s work.
Sensing and Reasoning
Authors: Boyle Deborah 
Published: December 2022

Abstract
Shepherd’s goal in Essays on the Perception of an External Universe is to prove, from facts about perceivers’ transitory sensations, that there is an independent, continuously existing world of external objects that cause those sensations. Since Shepherd’s arguments turn on claims about sensations, it is important to understand what she means by ‘sensation,’ as well as related terms like ‘perception,’ ‘idea,’ and ‘notion.’ This chapter surveys these key concepts in Shepherd’s philosophy of mind. It also explores her accounts of various mental faculties, including sensory perception (and her claim that motion is a sense), memory, imagination, will, and understanding. Her causal account of reasoning and her distinctive accounts of demonstrative and probable reasoning are also discussed and contrasted with Hume’s views.
Religion
Authors: Boyle Deborah 
Published: December 2022

Abstract
This chapter surveys various issues in philosophy of religion that Shepherd considers in her Essays on the Perception of an External Universe. It covers her views about whether or not there are ever good reasons to believe in reported miracles and her objections to Hume’s account of such beliefs; her teleological and cosmological arguments for belief in God; her views on the possibility and nature of an afterlife; and her explanation of divine causation, given her belief that all causation involves the synchronous mixing of qualities. The chapter ends with some speculation about connections between Shepherd’s beliefs and emanationism and Spinozism.
Economic Structure and Access
Authors: Dore Poornima , Narayanan K. 
Published: December 2022

AbstractIn this Chapter the definition and rationale of the ‘region’ as a unit of analysis is discussed, and among other things, the detailed methodology of calculating regional value added, calculating sectoral shares and also the diversity index etc. is explained. A deep discussion on data sources at the regional level as well as the analytical techniques that they lend themselves to which we use in later chapters, are explained here.
Inter-temporal Differences across Regions
Authors: Dore Poornima , Narayanan K. 
Published: December 2022

AbstractIn this Chapter it is argued that if there is indeed a typology of regions that is different in the two time periods 2004-05 and 2011-12, then which are those variables that actually account for these differences. A detailed discriminant analysis is carried out for a set of variables across both time periods, the results of which reveal certain distinguishing factors. Opportunities for reaping advantages of economies of Scale and scope, along with skills and access to finance emerge as important discriminants, highlighting the need for a dynamic policy making.
“More than a Contract”
Authors: Chettiar Teri 
Published: December 2022

Abstract
This chapter continues the examination of the rising value attributed to intimate family relationships in the post-1945 decades by focusing on the important role that marriage counseling and therapy services played in promoting its wide-ranging benefits for both individual emotional health and national wellbeing. The chapter explores the implications of state support for relationship therapy services and uncovers how the expansive social health objectives of marriage therapy pioneers actively contributed to the welfare-state project of creating a “classless” social democratic society. Citizens’ access to loving relationships were cast as the great social equalizer as marriage therapists argued that individuals were primarily shaped through their desire for emotional, rather than socio-economic, wellbeing. This chapter also investigates the unintended political effects of marriage therapy, revealing how therapists’ language and concepts shaped a new public discourse of relationship “breakdown” and provided persuasive (ostensibly scientific) arguments for liberalizing the divorce law. Tracking divorce reformers’ mobilization of psychiatric understandings of intimate relationships in framing and legitimizing their demands for change, I investigate the effects of the dissemination of this new body of psychosocial knowledge in shaping public expectations and related political discourses of emotional fulfilment and psychological freedom.
Inherently Unstable
Authors: Chettiar Teri 
Published: December 2022

Abstract
Chapter 6 investigates another set of activist campaigns prioritizing access to intimate relationships, but this time directed at the freedoms of young people: the sexual expression of teenagers and queer men under the age of twenty-one. It examines how the longstanding psychiatric pathologization of adolescence as a period of emotional instability became the basis for closing down a series of explosive controversies surrounding teenage sexuality in the 1970s. By the end of the decade, the democratic and emotionally enlightened “good society” had come to be equated with the guarantees of privacy and sexual freedom. I argue that this freedom, however, was rooted in associations between adulthood and emotional maturity and legitimated through its exclusion of children as the proper recipients of the protection of the state. The infantilization of adolescents and young queer men provided a compelling rationale for not offering consistent sex education in British schools and NHS-provided birth control to young women, as well as for maintaining age-based restrictions in the laws surrounding sexual consent.
“Home Is for Many a Very Violent Place”
Authors: Chettiar Teri 
Published: December 2022

Abstract
This chapter considers the surprising durability of the intimacy ideal in the face of the “discovery” of family violence in white middle-class families in the 1970s. This chapter explores influential exposés of the routineness of middle-class family violence produced by antipsychiatrists, second-wave feminists, and activists associated with the battered women’s refuge movement. It reveals that the mother-child relationship took on even greater emotional significance as the basis for a fulfilling private life despite political movements that attempted to destabilize other traditional normative views of gender roles. This chapter demonstrates the enduring preoccupation with emotional relationships in this era of privacy, especially spotlighting the intensified importance of mothers’ emotional labor and presumed natural capacity for emotional connection even though intimacy in families was increasingly exposed as having a dangerous dark side.
An Intellectual History of Federalism
Authors: Arban Erika 
Published: December 2022

Abstract
The chapter briefly retraces the intellectual history of federalism and offers an account of federalism from the point of view of constitutional theory. In the chapter, federalism is presented as a constitutional principle that advocates division of authority and dispersion of powers among different societal groups and organizations, to reflect what Elazar dubbed ‘self-rule’ and ‘shared rule.’ It is also construed as an umbrella term that includes different experiences. In fact, while the US federation emerged in 1787 is usually regarded as the quintessential classic federal model, in recent years federal principles and elements have been adapted to a variety of situations, blending centripetal and centrifugal forces, federal and non-federal experiences, in a process leading to always novel experimentations. The discussion of cities in federal constitutional theory—which lies at the core of this volume—is a compelling illustration of this recent intellectual evolution in federalism design. The existing literature on federalism and federal theory is truly gigantic and therefore it is impossible to treat it exhaustively in a very limited space. The present chapter will thus identify what the author believes are the intellectual milestones of federal history and theory (section II) before delving into the historical treatment (or lack thereof) of cities as federal constitutional entities or ‘units’ (section III).
Subsidiarity and the City
Authors: Cahill Maria , O’Sullivan Garry 
Published: December 2022

Abstract
It seems to be a near universal feature of the intellectual project of justifying enhanced formal and material autonomy for cities that adherents invoke subsidiarity and believe that it offers a presumptive endorsement of the case for city autonomy. This chapter examines the symbiotic interplay between subsidiarity and the city, by exploring four types of justifications for increasing city autonomy—the consistency argument, the expertise argument, the stake-holding argument, and the distinctiveness argument—and the extent to which they track with four models of subsidiarity—subsidiarity-as-federalism, subsidiarity-as-efficiency, subsidiarity-as-democracy, and subsidiarity-as-respect-for-distinctiveness. It will be argued that this reflective exploration yields important learning opportunities on both sides. For subsidiarity scholars, closer analysis of the concrete case of city autonomy exposes the dangers of eliding the differences between subsidiarity and federalism and between subsidiarity and efficiency, and showcases the surprising attractiveness of a model of subsidiarity that focuses on the distinctiveness of the (putative) decision-making level involved. For city scholars, deeper reflection on the challenges that subsidiarity scholarship poses to it will demand, first, greater clarity about how the city is to be defined and, second, greater specificity about the level of autonomy the city should bear.