Substantive Changes Research Articles

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers.

Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response. We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers. We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months. Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3-15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes. These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.

Traffic violator school masked convictions: California finally got it right

Introduction: The negative traffic safety impact of California’s prior traffic violator school (TVS) citation dismissal policy is well documented in past California TVS evaluations. Method: Using advanced inferential statistical techniques, the current study evaluated the substantive changes to California’s traffic violator school program as required by California Assembly Bill (AB) 2499. The program changes implemented by AB 2499 appear to be associated with a specific deterrent effect as evidenced by a reliable and statistically significant reduction in subsequent traffic crashes of those receiving a masked TVS conviction as opposed to a countable conviction. Results: The results suggest that this relationship exists primarily among TVS drivers with less elevated prior records. The change in status from a TVS citation dismissal to a TVS masked conviction has reduced the negative traffic safety impact of the TVS citation dismissal policy in effect prior to the implementation of AB 2499. Several recommendations are offered to enhance the positive traffic safety impact of the TVS program by further combining its educational elements with the state’s post license control program by way of the Negligent Operator Treatment System. Practical Applications: The findings and recommendations have implications to all states and jurisdictions utilizing pre-conviction diversion programs and/or demerit point systems associated with traffic violations.

High-resolution 1H NMR analysis of continuous and discontinuous thermo-oxidative susceptibility of culinary oils during frying at 180 °C.

Lipid oxidations products (LOPs) are reactive mutagenic and carcinogenic species known to be generated in thermally stressed culinary oils. Mapping the evolution of LOPs in culinary oils exposed to standard frying practices - both continuous and discontinuous thermo-oxidation - at 180 °C is vital to our understanding of these processes, and to the development of scientific solutions for their effective suppression. Modifications in the chemical compositions of the thermo-oxidised oils were analysed using a high-resolution proton nuclear magnetic resonance (1H NMR) technique. Research findings acquired showed that polyunsaturated fatty acid (PUFA)-rich culinary oils were the most susceptible to thermo-oxidation. Consistently, coconut oil, which has a very high saturated fatty acid (SFA) content, was highly resistant to the thermo-oxidative methods employed. Furthermore, continuous thermo-oxidation produced greater substantive changes in the oils evaluated than discontinuous episodes. Indeed, for 120 min thermo-oxidation durations, both continuous and discontinuous methods exerted a unique impact on the contents and levels of aldehydic LOPs formed in the oils. This report exposes daily used culinary oils to thermo-oxidation, and therefore, it permits assessments of their peroxidative susceptibilities. It also serves as a reminder to the scientific community to investigate approaches for suppressing toxic LOPs generation in culinary oils exposed to these processes, most notably those involving their reuse.

On Substantive Changes to Contracts Under the United Nations Convention on Contracts for the International Sale of Goods

First of all, it is important to clarify the premise that the most fundamental basis for the sale and purchase of goods between the international community and countries is in fact the contract for the sale and purchase of goods concluded between the buyer and the seller, and that this contract is the basis for the clarification of their rights and obligations between the parties and for the act of performance. The contract shall be formed on the basis of the act of offer and promise between the parties, so that the validity of the offer and promise has a direct influence on the formal formation of the contract and the subsequent act of sale and purchase of goods. National laws differ as to whether a promise must be identical to an offer. For example, in the common law system there is the well-known “mirror image principle”, which requires a high degree of conformity. Article 19 of the United Nations Convention on Contracts for the International Sale of Goods (CISG), however, provides for this in three main clauses. [i]Even though national laws and international treaties such as the CISG contain specific provisions on offers, promises and material changes to contracts, there is still much uncertainty in practice. This essay will extend the discussion of material change in contracts through a specific international trade case and will focus on the CISG provisions on material change in contracts and their content. Chapter 3 will provide reflections on material change based on the first two papers.

Shoulder arthroplasty device clearance: an ancestral network analysis.

The US Food and Drug Administration (FDA) oversees medical device regulation and oversight in the United States, and the majority of shoulder arthroplasty devices are cleared via the 510(k) pathway, in which a device demonstrates "substantial equivalence" to a previously cleared predicate. The purpose of this study was to determine an interconnected ancestral network of shoulder arthroplasty devices and determine equivalency ties to devices subsequently recalled by the FDA for design-related issues. The FDA 510(k) database was used to identify all legally marketed shoulder arthroplasty devices from May 28, 1976, to July 1, 2021. Direct predicate information obtained via clearance summary documents associated with each device was used to generate an ancestral genealogy network for all shoulder arthroplasty devices cleared between July 1, 2020, and July 1, 2021. FDA design recalls were analyzed, and the number of descendant devices was calculated for each recalled device. An evaluation of all 476 510(k) premarket notification pathway-cleared shoulder devices since 1976 identified 0-313 descendant devices for each. Eighty of these devices (16.8%) have since been recalled, of which 10 recalls were directly related to implant design issues. Furthermore, among 29 of the most recently cleared devices (July 1, 2020-July 1, 2021), 16 (55.2%) claim predicates devices that have subsequently been withdrawn from the market because of design-related failures. Shoulder arthroplasty devices are linked together via an interconnected FDA 510(k) equivalency approval network dating back to 1976 despite substantive changes in material specifications and device design, many of which have since been recalled. Many of the cleared modern devices claim predicates based on subsequently recalled prostheses.

Effect of moderate exercise on osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease, which can cause a series of symptoms including pain and functional limitation, thus severely decreasing quality of life. OA pathogenesis can be categorized into four levels, including risk factors, potential mechanisms, intraarticular degeneration phenotype, and substantive histological changes. Moderate exercise can alleviate OA at all levels of pathogenesis, while excessive exercise may have adverse effects. Based on rat-related original research, the parameters of moderate exercise and the effect of improving osteoarthritis have been comprehensively summarized. Based on the extensive randomized controlled trial studies, results show various moderate exercises can improve the symptom and prognosis of OA in clinical settings. This review gives an overview of the pathogenesis of OA and the mechanisms as well as clinical examples of moderate exercise treatment, aimed at providing rationale and evidence for moderate exercise in the treatment of OA to facilitate the provision of appropriate exercise therapy for OA patients.

Taking Rights Seriously? Recent Shifts in Procedural and Substantive Matters of the Thai Constitutional Court

The Thai Constitutional Court has recently dealt with more cases concerning constitutional rights such as those involving abortion and same-sex marriage, gaining widespread public attention similar to its many cases on political issues. This new development may show that the Court has now performed its role as a constitutional guardian and bulwark of rights. But the expansion of the caseload on rights may promote judicial activism and thus indicate a new strategy for the Court to be more powerful. This article looks at both the substantive changes in the jurisprudence of the Court as well as the procedural adjustments in recent court cases to determine the extent to which the Court has transformed itself to the ideal image of a great constitutional court in a comparative context. The Article analyzes all constitutional rights cases decided since 2019 to gauge the overall performance of the Court. Moreover, the Article also provides some examples of cases that seemingly protect constitutional rights but simultaneously expand the powers of the Court in the future. The analysis then suggests that while the Court might have facially helped protect more rights, it comes with a cost of a potentially even more active and political Court.

Diversity, Equity, and Inclusion: Advancing Curricular Development and Recruitment.

Currently, the increasing diversity of our society is poorly reflected in the urology workforce. In this review, we sought to address this disparity by highlighting key components involved in forming an academic urology department and training program that is focused on diversity, equity, and inclusion (DEI) as well as recruitment and retention of underrepresented in medicine (URiM) trainees and faculty. We identified obstacles and provided approaches to enhance the ability of a department in creating a DEI-based curriculum and recruitment strategy with a key focus on understanding and addressing unconscious biases and microaggressions in the workplace. Substantive changes in the level of diversity within the urologic community can be made through the organization of a structured approach to increasing DEI. It starts with a commitment from each department to form achievable goals surrounding early mentorship of URiM students and trainees, an inclusive curriculum that is rooted in DEI, and targeted benchmarks for recruitment and retention of diverse staff.

ATP-competitive and allosteric inhibitors induce differential conformational changes at the autoinhibitory interface of Akt1

Akt is a master regulator of pro-growth signaling in the cell. Akt is activated by phosphoinositides that disrupt the autoinhibitory interface between the kinase and pleckstrin homology (PH) domains and then is phosphorylated at T308 and S473. Akt hyperactivation is oncogenic, which has spurred development of potent and selective inhibitors as therapeutics. Using hydrogen deuterium exchange mass spectrometry (HDX-MS), we interrogated the conformational changes upon binding Akt ATP-competitive and allosteric inhibitors. We compared inhibitors against three different states of Akt1. The allosteric inhibitor caused substantive conformational changes and restricts membrane binding. ATP-competitive inhibitors caused extensive allosteric conformational changes, altering the autoinhibitory interface and leading to increased membrane binding, suggesting that the PH domain is more accessible for membrane binding. This work provides unique insight into the autoinhibitory conformation of the PH and kinase domain and conformational changes induced by Akt inhibitors and has important implications for the design of Akt targeted therapeutics.

Engineered tissue vascularization and engraftment depends on host model

Developing vascular networks that integrate with the host circulation and support cells engrafted within engineered tissues remains a key challenge in tissue engineering. Most previous work in this field has focused on developing new methods to build human vascular networks within engineered tissues prior to their implant in vivo, with substantively less attention paid to the role of the host in tissue vascularization and engraftment. Here, we assessed the role that different host animal models and anatomic implant locations play in vascularization and cardiomyocyte survival within engineered tissues. We found major differences in the formation of graft-derived blood vessels and survival of cardiomyocytes after implantation of identical tissues in immunodeficient athymic nude mice versus rats. Athymic mice supported robust guided vascularization of human microvessels carrying host blood but relatively sparse cardiac grafts within engineered tissues, regardless of implant site. Conversely, athymic rats produced substantive inflammatory changes that degraded grafts (abdomen) or disrupted vascular patterning (heart). Despite disrupted vascular patterning, athymic rats supported > 3-fold larger human cardiomyocyte grafts compared to athymic mice. This work demonstrates the critical importance of the host for vascularization and engraftment of engineered tissues, which has broad translational implications across regenerative medicine.

How Sanctions Led to Authoritarian Capitalism in Venezuela

After a deterioration of democratic conditions in Venezuela, in 2017 the United States intensified its sanctions imposed on the regime of Nicolás Maduro. The sanctions failed to topple the regime, but they accelerated the transformation of the Venezuelan economy. To counter the sanctions, Maduro carried out substantive economic policy changes, resulting in the emergence of a neo-patrimonial and authoritarian form of capitalism. In this new model, private ownership is the rule, and economic agents operate for profit. Yet there is frequent state intervention that denies individuals’ fundamental political and economic rights, and the purpose of laws and regulations is ensuring regime survival.

Substance and Style in the Prolife Discourse

This essay is directed to the prolife community and argues that the abortion discourse on Catholic campuses will be improved significantly if the prolife community more intentionally integrates specific substantive and stylistic changes regarding the ethics and politics of abortion. Substantively, the impasse in the discourse may be initially bridged by what many prolife and prochoice persons should generally agree on—that abortion is driven by vicious social structures and a broken moral culture. Abortion is primarily a socially-generated moral problem that requires a socially-generated moral solution. The prolife and prochoice communities can agree and potentially collaborate on solutions to this social crisis. In light of the social factors that drive abortion, the prolife community should take seriously the experiences of women who have abortions and express more compassion for them. This community all too often quickly dismisses the suffering of women and, instead, trains its attention nearly exclusively on the unborn child. Both the mother and unborn child are victims of injustice and are deserving of compassion and mercy. Stylistically, the mode of the prolife discourse should reflect its message. A message of charity for all persons should be communicated charitably. Dialoguing with love is opposed to the ‘culture warrior’ ethos that currently plagues our nation.

The impact of traumatic brain injury on economic productivity in the Caribbean

IntroductionTraumatic brain injury (TBI) is a significant cause of morbidity and mortality in the Caribbean as well as globally. Within the Caribbean, the prevalence of TBI is approximately 706 per 100,000 persons – one of the highest rates per capita in the world. Research questionWe aim to assess the economic productivity lost due to moderate to severe TBI in the Caribbean. Material and methodsThe annual cost of economic productivity lost in the Caribbean from TBI was calculated from four variables: (1) the number of people with moderate to severe TBI of working age (15–64 years), (2) the employment-to-population ratio, (3) the relative reduction in employment for people with TBI, and (4) per capita Gross Domestic Product (GDP). Sensitivity analyses were performed to evaluate whether the uncertainty of the TBI prevalence data result in substantive changes in the productivity losses. ResultsGlobally, there was an estimated 55 million (95% UI 53, 400, 547 to 57, 626, 214) cases of TBI in 2016 of which 322,291 (95% UI 292,210 to 359,914) were in the Caribbean. Using GDP per capita, we calculated the annual cost of potential productivity losses for the Caribbean to be $1.2 billion. Discussion and conclusionTBI has a significant impact on economic productivity in the Caribbean. With upwards of $1.2 billion lost in economic productivity from TBI, there is an urgent need for appropriate prevention and management of this disease by upscaling neurosurgical capacity. Neurosurgical and policy interventions are necessary to ensure the success of these patients in order to maximize economic productivity.

The Implementation of Micro-Credentials in Formal and Informal Learning: A Systematic Literature Review

When educational institutions across the globe closed because of the COVID-19 crisis, they rapidly had recourse to emergency remote teaching, online learning, and self-paced training. Such an unprecedented situation accelerated the movement and uptake on courses from online platforms such as Coursera, Udemy, etc. As such, modular learning was seen as a way for learners and professionals to keep on upskilling and reskilling themselves both in academic and professional areas. The recognition of the knowledge acquired, and competencies demonstrated by learners, via a new credentialing system, termed as micro-credentials, is seen as a novel, but ambitious approach that is being portrayed as a highly probable future of education systems. However, several research studies have been conducted in this area with little breakthrough or widescale implementation that has led to substantive changes in existing educational systems and models. This paper presents a systematic literature analysis to understand how micro-credentials concept has so far been implemented in educational contexts, its potential to be recognized as transferable credits in formal higher education and the technologies being implemented to store, stack and manage micro-credentials. The data collection process consisted of selecting articles published in the past ten years. The results show that although there is a growing interest in this research area, there is significant divide between applications and recognition of micro-credentials. Hence, this paper reports a summary of prior research conducted and help in identifying the gaps in research studies with respect to the implementation of micro-credential in formal and informal learning.

Strengthening health care in Canada post-COVID-19 pandemic

The purpose of this policy briefing is to examine our health care systems through the lens of the COVID-19 pandemic and identify how we can strengthen health care in Canada post-pandemic. The COVID-19 pandemic has provided compelling evidence that substantive changes to our health care systems are needed. Specifically, the pandemic has emphasized structural inequities on a broad scale within Canadian society. These include systemic racial and socioeconomic inequities that must be addressed broadly, including in the delivery of health care. We make recommendations about what we can do to emerge stronger from the pandemic. While these recommendations are not novel, how they are framed and contextualized differs because of the problems in our health care system that have been highlighted and exacerbated by the pandemic.The evidence is clear that socioeconomic circumstances, intergenerational trauma, adverse early life experiences, and educational opportunities are critical factors when it comes to health over the life course. Given the problems in the delivery of health care that the pandemic has revealed, we need a different approach. How health care was organized prior to the COVID-19 pandemic did not produce what people wanted and needed in terms of health care and outcomes. How do we emerge from COVID-19 with an effective, equitable, and resilient health care system for all Canadians? To address health inequities and emerge from the pandemic with strengthened health care in Canada, we must consider how Amartya Sen's capabilities framework on social well-being can be operationalized to achieve better health care and health outcomes. Specifically, we address the need to: strengthen primary care and improve access to primary care; utilize a community-embedded approach to care; and implement better integration across the care continuum, including integration between primary care and public health. Coherent governance and leadership that are charged with realizing benefits through collaboration will maximize outcomes and promote sustainability. Only when we provide access to high-quality culturally competent care that is centered around the individual and their needs will we be able to make true headway in addressing these long-standing health inequities.

Национальные интересы Китая: коннотации, иерархия, балансирование

The connotations of the interests of the PRC in the official scientific and political discourse during the period of the existence of the new Chinese state first transformed from class (jieji liyi, 1949–1978) to actually national (national-state – guojia liyi, 1979–2008), and then transition to “indigenous (core) national” (hexin guojia liyi, or simply “indigenous” – hexin liyi), and this emphasis became dominant after 2012. This process reflects substantive changes in the state’s strategy. At the same time, the spatial and geographical range of his interests was expanding – from a predominant focus on domestic needs to regional and global ones. Since the 12th Chinese Communist Party Congress of 1982 declared that China would adopt foreign policy according to its national interests, the term “national interests” has been frequently used in Chinese official documents. The problems of national interests in the Chinese academic community were first raised in 1987 at the Shanghai Scientific Conference on the Theory of International Relations. In 1995, Yan Xuetong published China’s first monograph on this subject, “Analysis of China’s National Interests”, on which he worked for two years (grant from the Chinese Academy of Contemporary International Relations) after returning from the United States, where he defended his doctoral dissertation. The publication of this book even sparked a “great debate” between young scholars and traditionalists about the normative requirements for writing papers. The article shows the dynamics of changes in the national interests of the PRC, their connotations and hierarchy both in academic discourse and in the practice of Chinese diplomacy (case of Russia and Ukraine).

Молодая семья как «ускользающий» социальный феномен в современных российских условиях

Introduction. Modern youth is included today in a variety of social institutions, within which their attitudes, identity values are formed. Sociological studies of recent decades clearly show that the family, despite all the variety of formal and substantive changes in modern institutions of family and marriage, occupies a leading place in the scale of value preferences of young Russians, transforming the matrimonial attitudes of young people and providing a complex mechanism of social integration. The multivariance and dynamism of modern family and marriage relations (cohabitation, changes in the age limits of marriage, changes in the limit of the duration of marriage, an increase in the number of remarriages, the absence of children in marriage, etc.) enhances the role and importance of individualized strategies for young people to enter this social institution, providing it has the opposite effect, in terms of further changes and transformations. Such a transformation, according to the authors, is typical for the modern institution of a young family, which, due to a number of interrelated trends, and in particular the trend of “postponed marriage”, may cease to be an actual social phenomenon that allows young people to use some state types of assistance and support provided for families. of this kind. Methods. As part of the work, an analysis of legal documents is carried out: the Federal Law “On Youth Policy in the Russian Federation”, the Federal Target Program «Housing» for 2015-2020, the State Program «Providing affordable and comfortable housing and utilities for citizens of the Russian Federation». The empirical basis of the work is: data from all-Russian studies and the results of the sociological study «Marriage age: preferences of young people in the city of Rostov-on-Don», conducted in 2021 (N=200). Results and its discussion. The legal acts available in the Russian Federation have now begun to fix clearer criteria for the term "young family". The authors of the article believe that changes in normative terminology are associated with a steady trend towards an increase in the average age of both the bride and groom upon marriage, which in turn is due to many factors: the individualization of romantic relationships, increased freedom of choice, the change in public regulators of matrimonial attitudes to economic. Despite an attempt to formulate certain criteria for the term "young family" in the legislative framework of the Russian Federation, the authors note that the transformation of marriage with the tendencies of individualism, delayed marriage, a period of self-realization and delayed, and sometimes completely unrealized reproductive functions of the family, leads to the fact that the phenomenon young family, in the form in which it exists today, in the conditions of Russian society becomes elusive.

FILE OF LIFE: OLDER ADULT PERSPECTIVES AND SUGGESTIONS TO INCREASE FOL USAGE

Abstract IntroductionIn a home emergency, an accurate patient medical history is vital for proper medical decision-making. One method to provide medical information in an emergency is through the FILE OF LIFE™ (FOL); a document distributed by local medical centers and public service organizations completed by community adults and placed on their refrigerator in a magnetic folder. To date, there was no known study, until this one, conducted with older adults to check the FOL design suitability for older adults; the goal of this project. MethodsOlder adults were recruited through the UNE COM Geriatrics Education Mentor (GEM) program for this pilot qualitative research. Twenty-one GEMs volunteered to participate in five 90-minute focus groups. Questions were specific for each section - Patient Identifiers, Emergency Contacts, Medical Data, Medical Conditions, Allergies, and Medical Insurance Information, and the usability of the FOL. Qualitative content analysis followed by NVivo 12+ analysis applied inter-rater reliability methods and changes for each FOL section were based on reaching data saturation. ResultsFILE OF LIFE™ comments (N=328) were coded to the following themes: Layout, Font Size, Spacing, and Section Ordering. Sections were edited accordingly with “Identifiers,” Medical Data, Medical Conditions, Allergies, and Emergency Contacts requiring substantive changes. Other minor changes were made throughout the form. ConclusionFurther research will ensure efficient usability by older adults and emergency response personnel. The FILE OF LIFE™, although a trusted resource for older community dwelling residents, has a chance to increase usability by incorporating the suggested changes from this research.

Варяги и Русь: особенности военного противостояния и взаимодействия (VI–XIV века)

The article is devoted to the study of medieval Scandinavian and domestic narrative sources for information about the peculiarities of the military confrontation and interaction between the Varangians and Ancient Rus. On the basis of the analyzed materials conclusions have been made about the necessity of applying the method of comparative analysis when considering medieval Nordic narrative sources, and also about the peculiarities and substantive changes of Russian-Scandinavian relations during the period VI–XIV centuries: the battles between the Varangians and Rus were fought both on land and at sea, across a vast geographical area; the analyzed sources show evidence of military interaction between the Varangians and Ancient Rus through the recruitment of individual detachments, military aid and dynastic alliances; the character of the military confrontation between the Varangians and Rus is traced as the principles of warfare change by the XIV century.

570. What’s the Harm? Development and Implementation of an Antimicrobial Stewardship Intervention Impact Score

Abstract Background Various metrics evaluate antimicrobial stewardship program (ASP) success, including utilization, cost savings, and guideline adherence. Patient safety initiatives are at the forefront of hospital metrics. No commonly applied ASP measures evaluate patient harm. Our objective was to develop and implement a novel scoring tool quantifying the impact of ASP interventions on prevention of patient harm. Methods This initiative was conducted at a 386-bed pediatric hospital with an ASP conducting prospective audit with feedback (PAF) rounds since 2008. ASP created a multidisciplinary subgroup to develop a scoring tool classifying interventions as low, moderate, and high impact. With low impact interventions, patient harm was unlikely, but opportunities existed for minor antimicrobial optimization. Moderate interventions had substantial room for optimization but still had low risk for patient harm. High impact interventions carried a substantial risk of patient harm due to high probability of an adverse drug event or due to poor outcomes from an inappropriate regimen. Using these principles, definitions for each level of impact were created for all ASP intervention categories (Table 1). ASP providers were trained on the tool and scored each intervention on daily PAF rounds. To improve objectivity, 2 ASP providers independently scored each intervention and discrepancies identified. Discrepancies were evaluated monthly, and the tool was modified. Results Between 11/9/21-3/31/22, ASP reviewed 2010 antimicrobial orders with 238 interventions made and scored for impact. Of these, 124 (52.1%) were low, 99 (41.6%) moderate, and 15 (6.3%) high impact. There were 26 scoring discrepancies identified which were discussed by the ASP subgroup. To further clarify definitions, there were 5 substantive definition changes and 4 minor modifications; most changes were made in 12/2021. Conclusion We describe here the successful implementation of a novel tool to score ASP interventions on stewardship impact and prevention of patient harm. Future directions include utilizing this tool to direct systematic ASP interventions, partnering with organizational patient safety, and engaging in a multi-institutional working group for further development. Disclosures All Authors: No reported disclosures.