2103. Emergency Department (ED) Stewardship: Stratifying ED Sepsis Order Sets by Penicillin (PCN) Allergy Severity

Background: The Surviving Sepsis Campaign Guidelines recommends administration of broad-spectrum antibiotics within 1 hour of sepsis diagnosis; electronic order sets drive antibiotic selection with pre-populated regimens based on the suspected infectious indication. Given the low rate of cephalosporin cross-reactivity in patients with a PCN allergy, we modified our ED sepsis order set (Images 1 and 2) to include cephalosporin options in patients with reported mild-to-moderate PCN reaction histories. This was a single-center, retrospective analysis evaluating the impact of this change on antibiotic prescribing and associated outcomes. Methods: An electronic medical record (EMR) report identified patients ≥18 years of age with a documented PCN allergy that received antibiotics via the ED sepsis order set from December 30, 2012 to September 28, 2013 (pre-intervention) and January 3, 2014 to July 18, 2015 (post-intervention). The primary objective was to compare antibiotic days of therapy (DOT) and length of therapy (LOT) between the pre- and post-groups. The secondary objectives included 30-day readmission and mortality, hospital length of stay (LOS), incidence of C. difficile within 6 months and documented hypersensitivity reactions. Bivariate analyses, with chi-square, Mann–Whitney U, and Poisson means test, were used. Results: A total of 180 patients (90 pre- and 90 post-intervention) were included. Demographics were similar between groups, with the exception of congestive heart failure (CHF) which was more prevalent in the post-intervention group (P = 0.039). Aztreonam, vancomycin, aminoglycoside, and fluoroquinolone DOTs were significantly reduced (P \u3c 0.001) while cephalosporin DOTs significantly increased (P \u3c 0.001) in the post-intervention group. There were no statistical differences in antibiotic LOT, 30-day readmission and mortality, hospital LOS, or incidence of C. difficile infection. For those patients that received cephalosporin antibiotics, there were no hypersensitivity reactions documented in the EMR. Conclusion: Stratifying ED sepsis order sets by PCN allergy history severity is a safe and effective intervention that reduces second-line antibiotics in PCN allergic patients presenting to the ED with suspected sepsis

Langdon Park Forest Patch: How three women turned their tree rescue efforts into a public-private partnership in community-based forest stewardship.

Early in the COVID-19 pandemic, community tree activists engaged in tree rescue activities in Washington, D.C.’s Langdon Park. They cleared non-native invasive vines and cataloged native tree species within the park’s 2.2-acre forest patch. Over the last 2+ years, they endeavored to share their story of forest stewardship, garnering support from district agencies and local non-profit Casey Trees. The ensuing collaboration has led to a healthier forest with greater community connection

Multiple Exportins Influence Thyroid Hormone Receptor Localization

The thyroid hormone receptor (TR) undergoes nucleocytoplasmic shuttling and regulates target genes involved in metabolism and development. Previously, we showed that TR follows a CRM1/calreticulinmediated nuclear export pathway. However, two lines of evidence suggest TR also follows another pathway: export is only partially blocked by leptomycin B (LMB), a CRM1-specific inhibitor; and we identified nuclear export signals in TR that are LMB-resistant. To determine whether other exportins are involved in TR shuttling, we used RNA interference and fluorescence recovery after photobleaching shuttling assays in transfected cells. Knockdown of exportins 4, 5, and 7 altered TR shuttling dynamics, and when exportins 5 and 7 were overexpressed, TR distribution shifted towards the cytosol. To further assess the effects of exportin overexpression, we examined transactivation of a TR-responsive reporter gene. Our data indicate that multiple exportins influence TR localization, highlighting a fine balance of nuclear import, retention, and export that modulates TR function

Outcome Measures in Rheumatology - Interventions for medication Adherence (OMERACT-Adherence) Core Domain Set for Trials of Interventions for Medication Adherence in Rheumatology: 5 Phase Study Protocol

Background: Over the last 20 years, there have been marked improvements in the availability of effective medications for rheumatic conditions such as gout, osteoporosis and rheumatoid arthritis (RA), which have led to a reduction in disease flares and the risk of re-fracture in osteoporosis, and the slowing of disease progression in RA. However, medication adherence remains suboptimal, as treatment regimens can be complex and difficult to continue long term. Many trials have been conducted to improve adherence to medication. Core domains, which are the outcomes of most relevance to patients and clinicians, are a pivotal component of any trial. These core domains should be measured consistently, so that all relevant trials can be combined in systematic reviews and meta-analyses to reach conclusions that are more valid. Failure to do this severely limits the potential for trial-based evidence to inform decisions on how to support medication adherence. The Outcome Measures in Rheumatology (OMERACT) - Interventions for Medication Adherence study by the OMERACT-Adherence Group aims to develop a core domain set for interventions that aim to support medication adherence in rheumatology. Methods/design: This OMERACT-Adherence study has five phases: (1) a systematic review to identify outcome domains that have been reported in interventions focused on supporting medication adherence in rheumatology; (2) semi-structured stakeholder interviews with patients and caregivers to determine their views on the core domains; (3) focus groups using the nominal group technique with patients and caregivers to identify and rank domains that are relevant to them, including the reasons for their choices; (4) an international three-round modified Delphi survey involving patients with diverse rheumatic conditions, caregivers, health professionals, researchers and other stakeholders to develop a preliminary core domain set; and (5) a stakeholder workshop with OMERACT members to review, vote on and reach a consensus on the core domain set for interventions to support medication adherence in rheumatology. Discussion: Establishing a core domain set to be reported in all intervention studies undertaken to support patients with medication adherence will enhance the relevance and the impact of these results and improve the lives of people with rheumatic conditions.The OMERACT-Adherence Group receives funding from OMERACT, which will be used to support a patient research partner in the OMERACT-Adherence Group to attend the OMERACT conference. OMERACT (http://www.omeract.org, contact: secretariat [email protected]) is the primary sponsor responsible for approving the initiation and overviewing the ongoing progress and management of the study. OMERACT mentors overview the design and conduct of the studies, including the interpretation of data and preparation, and review and approval of manuscripts. The following funding organisations had no role in the design and conduct of the studies; collection, management, analysis and interpretation of the data; or preparation, review or approval of manuscripts. AK is supported by the Arthritis Australia Scholarship funded by the Allan and Beryl Stephens Grant from the Estate of the Late Beryl Stephens. AT is supported by a National Health and Medical Research Council Fellowship (1037162). RC’s employer, the Parker Institute, Bispebjerg, and Frederiksberg Hospital, is supported by a core grant (OCAY-13-309) from the Oak Foundation. Phases 1–3 of the OMERACT-Adherence study were funded by a 2018 Arthritis Australia project grant (major funder), and a private research grant provided by Professor Stephen Hall

Comparing Internalization of Appearance Ideals and Appearance-Related Pressures Among Women from the United States, Italy, England, and Australia

Researchers have observed variation in levels of body image disturbance and eating pathology among women from different Western countries. Examination of cross-cultural differences in the established risk factors (i.e., thin-ideal internalization, muscular-ideal internalization, and appearance pressures from family, peers, and media) for negative outcomes may help to elucidate the prominence of specific risk factors within a given Western society and guide associated interventions. Women from the United States (US), Italy, England, and Australia completed the Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4). Analysis of covariance controlling for age and BMI indicated significant cross-country differences for all SATAQ-4 subscales. Results typically indicated higher levels of appearance-ideal internalization and appearance pressures in the US and lower levels in Italy; however, associated effect sizes were generally small. A medium effect of country was observed for peer-appearance pressures, which were highest in the US compared with all other countries. Repeated-measures analysis of variance and paired samples t tests conducted within each country identified thin-ideal internalization and media appearance pressures as the predominant risk factors for all four countries. Overall, findings suggest more cross-country similarities than differences, and highlight the importance of delivering interventions to address thin-ideal internalization and media appearance pressures among women from Western backgrounds

Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry

Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. Epub 2023 Jun 1.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227232/Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real-world” setting. Untreated lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.Dr Martin is supported by grants/contracts from the American Heart Association (20SFRN35380046, 20SFRN35490003, 878924, and 882415), Patient‐Centered Outcomes Research Institute (PCORI) (ME‐2019C1‐15328), National Institutes of Health (NIH) (R01AG071032 and P01 HL108800), the David and June Trone Family Foundation, Pollin Digital Health Innovation Fund, and Sandra and Larry Small; Dr Knowles is supported by the NIH through grants P30 DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236; and by a grant from the Bilateral Science Foundation. Dr Linton is supported by NIH grants P01HL116263, HL148137, HL159487, and HL146134.info:eu-repo/semantics/publishedVersio

Salve Regina University Act on Climate: Strategic Plan for the University to Reach State Carbon Neutrality Goals

In order to become more sustainable and meet the mandate set by the 2021 Rhode Island Act on Climate law (RI General Law §42-6.2), Salve Regina University must work to reach net-zero greenhouse gas emissions by the year 2050. Action to meet these standards begins now and must be continually built upon to ensure that Salve Regina University, as leader in Rhode Island, is always working for a more sustainable future. Throughout the Spring 2022 semester, students of the BIO-140: Humans and Their Environment course instructed by Dr. Jameson Chace have researched ways in which Salve Regina can begin on the path to zero greenhouse gas emissions today. By focusing on change in the areas of energy, transportation, food, financial investments, and sequestration, Salve Regina can reduce the greenhouse gas emissions of today for a more sustainable tomorrow. Recommendations are broken into three time periods. Action for today to achieve by 2030 include improving energy efficiency, installing the first electric vehicle (EV) parking/charging stations, increasing carbon sequestration, reducing beef in the campus diet, and assessing the carbon impact of university financial holdings. Actions to be initiated soon and to be achieved by 2040 include shifting away from natural gas heating when system renewals take place, increasing EV parking to meet rising demand, during turnover replace current university vehicles with electric or hybrid, continuing with sequestration efforts on campus, begin phasing out high carbon diet items, and by 2040 the university investment portfolio should be carbon neutral. If carbon neutrality can be reached by 2050 the most challenging aspects of campus life that need to change will require planning now and thoughtful implementation. The class in 2022 envisions a campus in 2050 where solar lights illuminate campus and buildings through the night, all university vehicles and most faculty and staff vehicles are electric and are found charging during the day at solar powered charging stations, dining services in Miley supports community agriculture and includes incentives for meatless and low carbon meal plans, the university has become a leader in low carbon/green market investing demonstrating how careful planning can reap high returns, and carbon sequestration on campus grounds has maximized such that off campus carbon offsets are established with local land trusts to complete the carbon neutrality goals. In doing so no only will the university be recognized as a state-wide leader in climate action, but will also be a global leader in working towards a world that is more harmonious, just, and merciful.https://digitalcommons.salve.edu/bio140_arboretum/1033/thumbnail.jp

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease