bluuebunny/crossref_metadata_2025 huggingface dataset:
679. In vitro Activity of Cefiderocol (CFDC), a Novel Siderophore Cephalosporin, Against Difficult-to-Treat-Resistant (DTR) Gram-Negative Bacterial Pathogens From the Multi-National Sentinel Surveillance Study, SIDERO-WT (2014–2017)
Authors: Longshaw Christopher , Tsuji Masakatsu , Hackel Meredith M , Sahm Daniel F , Yamano Yoshinori
Published: October 2019

Background

DTR organisms are defined as nonsusceptible to all high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems, and quinolones), leaving physicians with limited first-line treatment options. Analyses of electronic health records have shown that patients with DTR Gram-negative bacterial infections are more likely to receive inappropriate antibiotic therapy, have longer hospital stay and increased risk of mortality. CFDC is a novel parenteral siderophore cephalosporin with potent activity against aerobic Gram-negative pathogens, including carbapenem-resistant strains. We evaluated the in vitro activity of CFDC and comparators against DTR pathogens collected by the SIDERO-WT surveillance study.

Methods

A total of 30,459 clinical isolates of Gram-negative bacilli were systematically collected from United States, Canada, and 11 EU countries during 2014–2017. MICs were determined by broth microdilution for a panel of 7 antibiotics, including CFDC, ceftazidime–avibactam (CZA), ceftolozane–tazobactam (C/T), colistin (CST), cefepime (FEP), meropenem (MEM), and ciprofloxacin (CIP) according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller–Hinton broth (CAMHB) except CFDC, for which iron-depleted CAMHB was used. Susceptibility was determined according to CLSI interpretive breakpoints except CST, where EUCAST breakpoints were used. DTR pathogens were defined as being nonsusceptible to FEP, MEM, and CIP according to CLSI breakpoints.

Results

Among 30,459 Gram-negative isolates collected between 2014 and 2017, 9.3% were nonsusceptible to FEP, MEM, and CIP and could be defined as DTR. DTR was most frequently observed in Acinetobacter spp. (55.5%), followed by Burkholderia spp. (19%), Pseudomonas aeruginosa (9.5%), and Enterobacterales (2.7%). Of the 1,173 Stenotrophomonas maltophilia tested, 97% had MEM MIC of ≥8 mg/L; however, only 2.9% could be defined as DTR. Cefiderocol was the most active antibiotic tested against DTR isolates with 94.5% DTR-Acinetobacter spp., 98.3% DTR-P. aeruginosa, and 99.8% DTR-Enterobacterales susceptible (Table 1).

Conclusion

CFDC demonstrated potent activity against DTR Gram-negative pathogens with limited first-line treatment options.

Disclosures

All authors: No reported disclosures.
704. Incidence and Patient Outcomes of S. aureus Isolates from Acute Bacterial Skin and Skin Structure Infections (ABSSSI) with High Iclaprim MIC values in Phase 3 REVIVE Trials
Authors: Huang David B , Charrier Cedric , Le Bras Chloe , Hawser Stephen , Noviello Stephanie S
Published: October 2019

Background

The incidence and outcomes of patients with S. aureus isolates with an iclaprim MIC >8 µg/mL, a concentration that is not systemically achievable, were determined among patients from two Phase 3 studies for the treatment of ABSSSI, REVIVE-1 and -2.

Methods

REVIVE-1 and REVIVE-2 studies were 600-patient, double-blinded, randomized (1:1), active-controlled trials among patients with ABSSSI that compared the safety and efficacy of iclaprim 80 mg fixed dose with vancomycin 15 mg/kg (adjusted for renal function), both administered intravenously over 2 hours every 12 hours for 5–14 days. Patients had a bacterial skin infection suspected or confirmed to be due to a Gram-positive pathogen with a lesion size ≥75 cm2. An early clinical response (ECR) was defined as a ≥20% reduction in lesion size compared with baseline at the early time point (ETP) 48–72 hours after the start of administration of the study drug in the intent-to-treat (ITT) population. A clinical cure, defined as complete resolution of all signs and symptoms of ABSSSI was measured at the end of therapy (EOT) and test of cure (TOC) visit, 7–14 days after the last dose of study drug. At baseline, EOT and TOC visits, ABSSSIs were sampled for microbiological culture and broth microdilution susceptibility testing conducted in accordance with CLSI M7.

Results

The incidence of culture confirmed S. aureus isolates among patients with ABSSSI with an iclaprim MIC >8 µg/mL was 2.0% (16/790). Six were MSSA and 10 were MRSA. The clinical outcomes of these infections included ECR of 63% (10/16), EOT response of 81.3% (13/16) and the TOC response of 75% (12/16). For microbiological outcomes of these infections, the end of therapy response was 92.9% (13/14) and the test of cure response was 92.3% (12/13). In comparison, there was less variation in vancomycin MICs among the S. aureus isolates. For patients who were randomized to vancomycin and had a pathogen identified from their ABSSSI, the pooled ECR was 82.6% (242 of 293) at a vancomycin MIC of 0.5–1 µg/mL and one isolate from a patient with ECR had a MIC of 2 µg/mL.

Conclusion

Patients receiving iclaprim had good clinical and microbiological responses against S. aureus isolates with an iclaprim MIC >8 µg/mL, which are uncommon (2.0%).

Disclosures

All authors: No reported disclosures.
758. High-Throughput Mining of Electronic Medical Records Using Generalizable Autonomous Scripts
Authors: Rochat Ryan H , Demmler-Harrison Gail J
Published: October 2019

Background

The electronic medical record (EMR) has become a modern compendium of health information, from broad clinical assessments down to an individual’s heart rate. The wealth of information in these EMRs hold promise for clinical discovery and hypothesis generation. Unfortunately, as these systems have become more robust, mining them for relevant clinical information is hindered by the overall data architecture, and often requires the expertise of a clinical informatician to extract relevant data. However, as the information presented to the clinician through the digital workspace is derived from the core EMR database, the format is well structured and can be mined using text recognition and parsing scripts.

Methods

Here we present a program which can parse output from Epic Hyperspace®, generating a relational database of clinical information. To facilitate ease of use, our protocol capitalizes on the familiarity of Microsoft Excel® as an intermediary for storing the raw output from the EMR, with data parsing and processing scripts written in SAS V9.4 (Cary, North Carolina).

Results

As a proof of concept, we extracted the diagnosis codes and standard laboratories for 190 patients seen in our Congenital Cytomegalovirus Clinic at Texas Children’s Hospital in Houston, Texas. Manual extraction of these data into Microsoft Excel® took 1 hour, and the scripts to parse the data took less than 5 seconds to run. Data from these patients included: 3800 ICD-10 codes (along with their metadata) and 33,000 individual laboratory values. In total, more than 850,000 characters were extracted from the EMR using this technique. Manual review of 10 randomly selected charts, found the data in perfect concordant with the EMR, a direct reflection of the fidelity of the parsing scripts. On average, an experienced user was able to enter three ICD-10 codes each minute, and six individual laboratory values per minute. At best, this same process would have taken at least 110 hours using a conventional chart review technique.

Conclusion

High-throughput data mining tools have the potential to improve the feasibility of studies dependent upon information stored in the EMR. When coupled with specific content knowledge, this approach can consolidate months of data collection into a day’s task.

Disclosures

All authors: No reported disclosures
1005. The Antibiotic Optimization DOOR: Refining Assessment of Antibiotic Therapy with Desirability of Outcome Ranking
Authors: Smoke Steven , Patel Vishal , Leonida Nicole , DeVivo Maria
Published: October 2019

Background

Desirability of outcome ranking (DOOR) is a novel methodology for incorporating multiple outcomes into a single value to more comprehensively compare therapeutic strategies. Its primary application has been limited to antibiotic clinical trials, incorporating treatment success and antibiotic toxicity into a single measure. We describe the application of DOOR methodology to a retrospective study evaluating antibiotic optimization.

Methods

This was a single-center, retrospective quasi-experimental study conducted at an academic medical center evaluating the impact of prospective pharmacist review of rapid molecular diagnostic testing (RDT) of blood cultures on antibiotic optimization. Two 8-week time periods were evaluated, corresponding to RDT implementation prior to prospective pharmacist review (RDT-only) and RDT with prospective pharmacist review (RDT-PPR). Patients with a positive blood culture who were not on optimal therapy at the time of gram stain were included in the study. Outcomes included the percentage of patients who received optimal therapy, time to optimal antibiotic therapy, and percentage of patients who had therapy de-escalated. An antibiotic optimization DOOR was created with 3 ordinal ranks. The most desirable outcome, rank one, was patients receiving optimal therapy with no missed de-escalation opportunities. Rank two was patients receiving optimal therapy with a missed de-escalation opportunity. The least desirable outcome, rank three, consisted of patients not receiving optimal antibiotic therapy. Time to optimal therapy was used as a tiebreaker for patients in ranks one and two.

Results

A total of 19 and 29 patients were included in the pre and post-intervention periods, respectively. The percentage of patients reaching optimal therapy was 84% (16/19) and 97% ([28/29], P = 0.16). Median time to optimal therapy was 30:28:26 and 22:40:17 (P = 0.32), respectively. DOOR analysis indicated that the probability of a better outcome for the RDT-PPR group than the RDT-only group was 58% (95% CI 54–62).

Conclusion

In this small retrospective study, the use of a novel composite methodology identified the benefit of an intervention that was not detected by standard comparison of individual outcomes.

Disclosures

All authors: No reported disclosures.
1033. Effectiveness of a Physician-Driven Automated Antibiotic Time Out in the Setting of Gram-negative Bacteremia
Authors: Mohayya Sana , Narayanan Navaneeth , Cimilluca Daniel , Vaidya Parth , Malanowski Alexander , Bhowmick Tanaya
Published: October 2019

Background

In an effort to minimize complications associated with over-utilization of antibiotics, many antimicrobial stewardship programs have incorporated an antibiotic time out (ATO). Despite the increasing adoption of the ATO, limited data are available to support its effectiveness. This study was designed to assess the impact of an automated ATO integrated into the electronic medical record (EMR) on the rate of antibiotic modification in patients receiving broad-spectrum antibiotic(s) for Gram-negative bacteremia (GNB).

Methods

This was a single-center retrospective cohort study of inpatients from January 2017 to June 2018 conducted at a large academic medical center. ATO was implemented on October 31, 2017. Adult patients with GNB who received at least 72 hours of a systemic antibiotic were included. Patients with neutropenia or polymicrobial infections were excluded. The primary outcome was the proportion of patients who received a modification of therapy within 24 hours of final culture results. Secondary outcomes included modification at any point in therapy, time to modification of therapy, time to de-escalation, and days of therapy of broad-spectrum antibiotics.

Results

There was a total of 88 patients who met inclusion criteria, 37 patients pre-ATO and 51 patients post-ATO. The primary outcome of modification of therapy within 24 hours of final culture results was not significantly different for patients in the pre-ATO and post-ATO groups (19% vs. 20%, P = 0.94, respectively). The secondary outcome of modification of therapy at any point in therapy was not significantly different between the two groups (62% vs. 66%, P = 0.67). Of the 47 patients who received a modification of therapy, the mean time to modification was significantly shorter in the post-ATO group (52.8 hours vs. 45.26 hours, P < 0.05,). All other secondary outcomes were not significantly different between study groups.

Conclusion

The ATO alert was not associated with a higher rate of antibiotic modification within 24 hours of culture results in patients with GNB, although there was a significant reduction in the time to antibiotic modification. Further efforts are needed to improve the time to modification and optimize antibiotic prescribing practices.

Disclosures

All authors: No reported disclosures.
1037. A Pharmacist-Driven 48 Hour Antibiotic Time Out Pilot at a Large Academic Medical Center
Authors: Carlson Travis J , Ryan Russo Hannah , Phe Kady , Al Mohajer Mayar
Published: October 2019

Background

The Centers for Disease Control and Prevention published The Core Elements of Hospital Antibiotic Stewardship Programs in 2014, which recommended that all clinicians perform an antibiotic time out (ATO) after 48 hours. The best methods to operationalize these recommendations remain unclear. Given our information technology barriers, we developed a targeted, pharmacist-driven, 48 hour ATO pilot.

Methods

This pre-post intervention pilot study included hospitalized adults admitted to one of the four wards between 5/1/18 and 6/30/18. Patients who received ≥48 hours of broad-spectrum intravenous antibiotics (vancomycin, piperacillin–tazobactam, cefepime, a carbapenem, or a fluoroquinolone) were prospectively identified via TheraDoc (Premier Inc., Charlotte, NC). An infectious diseases (ID) trained pharmacist reviewed patients on a daily basis during June. The primary outcome was days of therapy (DOT), which was assessed with Spearman’s rank-order correlation. All P-values were from 2-sided tests, and results were deemed statistically significant at P < 0.05.

Results

A total of 151 unique patients were identified during the study period. The most common antibiotic indications were skin and soft-tissue infection (31.1%), urinary tract infection (22.5%), and intraabdominal infection (22.5%). An ID physician was consulted on 59% of patients. The pharmacist reviewed an average of 7 patients (3 unique) each day during the intervention month. A total of 27 recommendations were made with 15 (56%) being accepted. The most common recommendations were to de-escalate therapy (n = 8), stop antibiotics (n = 6), and add a stop date to the antibiotic order (n = 4). DOT in the pre- and post-intervention period did not differ (P = 0.28).

Conclusion

A month-long, targeted, pharmacist-driven, 48 hour ATO pilot was unable to demonstrate a reduction in DOT. Furthermore, only 56% of pharmacist recommendations were accepted despite targeting low-acuity infections, which may have limited our ability to observe a reduction in DOT. Larger studies are warranted to further evaluate how ATOs influence DOT over time.

Disclosures

All authors: No reported disclosures.
1042. Antibiotic Stewardship Program (ASP) Implementation of Short-course Antimicrobials for Low-Risk Enterobacteriaceae Blood Stream Infection (EBSI) at a Tertiary Care Center
Authors: Alex Viehman J , Scott Gordon , Goshorn Eli S , Volpe Peter , Marini Rachel V , McCreary Erin K , Nguyen Minh-Hong
Published: October 2019

Background

Literature demonstrates short course (e.g., 7 days) of antibiotic therapy for EBSI is appropriate in low-risk patients. Real-world experience with the implementation of this approach is not known.

Methods

In January 2019, a prospective ASP pathway was implemented to review all ESBI. The ASP contacted treatment teams of patients (patients) with low-risk ESBI between day 4–6 of antibiotic therapy to recommend short-course antimicrobial therapy (SC, ≤10 days). Low-risk ESBI was defined as: (1) venous catheter-associated infection (with removal), or an uncomplicated urinary tract infection (UTI), and 2) absence of: organ transplant, polymicrobial or persistent bacteremia ( ≥3d), or lack of improvement at 72h. Controls were pre-intervention patients with low-risk EBSI between July 2016-December 2017. Carbapenem-resistant isolates were excluded; multi-drug-resistant (MDR, ≥3 class acquired resistance) and extended-spectrum β-lactamase (ESBL) bacteria were included.

Results

Pre-intervention, 107 patients met low-risk ESBI criteria. In the intervention period, 15 patients had low-risk ESBI. The ASP pathway was executed in 13/15 patients (87%) with an 85% success rate. Charlson Comorbidity Index scores and Pitt Bacteremia Scores were similar pre- and post-intervention. The post-intervention group was older (median 71y vs. 63y, P = 0.02). Otherwise, clinical characteristics did not differ pre- and post-intervention: cirrhosis (8 vs. 13%), renal failure (4% vs. 0%), ICU admission (29% vs. 33%) and BSI with ESBL or MDR bacteria (8% vs. 7%) and (21% vs. 20%). UTI was the most common source pre- and post-intervention (61% and 73%) Time to active therapy did not differ (median 0.15d vs. 0.12d). The median duration of active therapy for ESBI was 15d pre-intervention and 8d post-intervention (P < 0.001). SC rate improved from 11% to 67% post-intervention. There was no significant difference in recurrence (2% vs. 0%), mortality (2% vs. 0%) or readmission rates (25% vs. 20%) at 30d.

Conclusion

A multidisciplinary ASP pathway for low-risk ESBI resulted in the decreased duration of antimicrobial therapy without increased rates of recurrence, readmission, or morality at 30d. SC therapy was also effective for BSI due to MDR or ESBL producing bacteria.

Disclosures

All authors: No reported disclosures.
1051. The Use of Survey-Driven Feedback to Improve Antimicrobial Stewardship Efforts at a Single Center
Authors: Albarillo Fritzie S , Joyce Cara J , Santarossa Maressa
Published: October 2019

Background

Antimicrobial stewardship (AS) efforts have led to improved patient outcomes, reduction in unnecessary costs, and decrease in antimicrobial resistance (AR). Loyola University Medical Center (LUMC) is a quaternary care system that has primarily employed a formulary restriction and preauthorization process as the foundation of its Antimicrobial Stewardship Program (ASP).

Methods

In January 2018, a voluntary online survey was created and disseminated to all providers at LUMC to evaluate their baseline knowledge and perception of AS and AR, as well as to solicit feedback on current AS practices at LUMC. Based on the results of the survey, our AS team implemented the following changes to the AS program: removed prior-authorization of cefepime, piperacillin–tazobactam and vancomycin; required documentation of antimicrobial indications and duration upon order entry in the electronic medical record; and provided education to all providers via newsletters and lectures. In January 2019, a second survey was distributed to all providers with the primary goal of evaluating changes in the providers’ knowledge and perception of AS and AR post-program modifications. The secondary goal was to gather feedback on the major changes we have implemented in our program.

Results

A total of 167 providers completed the first survey and 173 completed the second survey. Over 95% of providers were aware that inappropriate use of antimicrobials can be harmful to patients, and that AS can decrease AR. Unfamiliarity with AS practices remains an issue. More than half agreed that unrestricting antibiotics improved their workflow, though almost half agreed that it led to inappropriate use by providers in general but not their own. Finally, most providers agreed that documenting indications and duration of antibiotics facilitated antibiotic optimization with no interference in their workflow.

Conclusion

Hospital-specific surveys on providers’ perception and knowledge on AS and AR can be used to guide future ASP interventions, as well as to evaluate the effectiveness of these interventions. Our ASP at LUMC implemented strategies to improve antimicrobial utilization based on our providers’ feedback. Our team will continue to use surveys to further guide our AS efforts.

Disclosures

All authors: No reported disclosures.
1090. Practicing Antimicrobial Stewardship: De-escalating Empiric Antibiotics in Patients with Acute Myelogenous Leukemia and Neutropenic Fever
Authors: Fuller Risa , Moshier Erin , Jacobs Samantha E , Tremblay Douglas , Lancman Guido , Coltoff Alexander , Caro Jessica , Mascarenhas John , Rana Meenakshi
Published: October 2019

Background

In the era of increased antibiotic resistance, minimizing the use of broad-spectrum antibiotics is essential. We sought to determine whether there was a difference in risk of recurrent fever in patients with acute myelogenous leukemia (AML) and neutropenic fever without an identifiable source in which antibacterials were de-escalated prior to neutrophil recovery compared with those that continued until recovery.

Methods

We performed a retrospective chart review of adult patients with AML undergoing induction chemotherapy at Mount Sinai Hospital in New York, NY from 2009–2017. Neutropenic fever was defined as a temperature of 100.4°F for 1 hour or single temperature of 101°F in a patient with an absolute neutrophil count (ANC) of less than 500 cells/μL. Febrile patients were treated with cefepime, piperacillin–tazobactam, or a carbapenem. De-escalation was defined as changing from one of these antibiotics to antibacterial prophylaxis such as levofloxacin, or discontinuing antibiotics. The primary outcome was recurrent neutropenic fever. Secondary outcomes were adverse events related to antibiotics, intensive care unit (ICU) transfer, and all-cause mortality.

Results

Of 390 AML patients undergoing induction chemotherapy, 135 had a neutropenic fever; of whom, 77 had no identifiable infectious source. Of those 77, 38 had antibiotics de-escalated prior to ANC recovery (“short”) and 39 had antibiotics continued until ANC recovery or discharge (“long”). Demographics were similar (Table 1). The median number of antibiotic days for the first fever was 9 in the short group and 15 in the long group (P = 0.0008) (Table 2). Risk of recurrent fever was 46% lower in the short group compared with the long group (hazard ratio 0.54, 95% CI: 0.34–0.88; P = 0.01). There was no significant difference in ICU transfer (P = 0.11) and in-hospital mortality (P = 0.36) between the short and long groups (Table 2). There were 7 adverse drug outcomes, 2 in the short group and 5 in the long group (Table 3).

Conclusion

Antibiotic de-escalation in AML patients with neutropenic fever with no identifiable infectious source was associated with a lower rate of recurrent fever without affecting ICU transfer, adverse drug events, and death. Physicians should consider de-escalation prior to ANC recovery in the appropriate setting.

Disclosures

All authors: No reported disclosures.
1128. Knowledge, Attitudes and Perceptions about Antibiotic Stewardship (AS) Programs among Neonatology Trainees
Authors: Akinboyo Ibukunoluwa C , Mukhopadhyay Sagori , Dukhovny Dmitry , Young Rebecca R , Puopolo Karen , Guzman-Cottrill Judith
Published: October 2019

Background

Antibiotic stewardship (AS) is a fundamental aspect of medical training. Neonatal Intensive Care Units (NICU) often have unique stewardship needs as they are ideal settings for the emergence and spread of drug-resistant bacteria. Assessing neonatology fellowship trainees’ knowledge and perceptions will highlight deficits in AS education and inform future curriculum development.

Methods

Prospective electronic survey study, distributed by Accreditation Council for Graduate Medical Education (ACGME) program directors to neonatology fellows in the United States over 4 months (January to April 2018). The objective was to assess neonatology fellows’ knowledge, attitudes and perceptions about AS to inform sustainable NICU-specific AS programs.

Results

Of 99 programs and 700 fellows, 159 respondents (23%) from 40 neonatology training programs (40%) responded to the survey and 139 (87%) provided complete responses. Respondents were equally spread across all 3 years of training

Seventy-two percent confirmed an institutional AS program existed, yet, only 33% were able to identify the components of AS programs and 66% either did not or were unsure if they had received AS training during fellowship. Furthermore, only 51% identified the appropriate empiric antibiotic for neonatal meningitis and 12% identified optimal methicillin-susceptible Staphylococcus aureus (MSSA) treatment while answering clinical case study questions. Notably, fellowship training year was not significantly related to the proportion of incorrect responses (P = 0.40).

Small group sessions were identified as the best teaching format (35%). This was followed by audit and feedback of individual prescribing behavior and didactic lectures which had an equal proportion of respondents (22%). Seventy-eight percent of respondents preferred a trainee-led AS program targeting necrotizing enterocolitis, antifungal prophylaxis and appropriate surgical prophylaxis.

Conclusion

Antibiotic stewardship is a critical part of physician training. While most institutions have a stewardship program, a dedicated curriculum incorporating small group sessions and didactics may be beneficial for educating neonatology trainees.

Disclosures

All authors: No reported disclosures
1130. Vancomycin Use in Pediatric Severe Sepsis at a Freestanding Children’s Hospital
Authors: Islam Shamim M , Yi Stacie M , Miller Anna , Sandhu Gurjot , Hassinger Amanda
Published: October 2019

Background

Surviving Sepsis Campaign guidelines recommend antibiotics be administered within 1 hour of severe sepsis (SS) onset, but do not suggest which agents to give. Vancomycin (VAN) is often chosen as empiric therapy for severe sepsis (SS) in children without evidence of the prevalence or risk factors for infections requiring VAN. As VAN is associated with significant nephrotoxicity, this study was performed to measure the risk-benefit ratio of empiric VAN use in pediatric sepsis.

Methods

This was a retrospective study of children with SS between 1/1/2015 to 6/30/2018 at the Women and Children’s Hospital of Buffalo, as captured by billing data and sent to state Department of Health for mandated reporting. SS cases were assessed for risk factors for Gram-positive infections, including presence of a central venous line (CVL) or other invasive device; history of MRSA infection or nasal colonization within the last 2 years; skilled nursing facility (SNF) residence; and prolonged hospitalization of >1 month. Invasive infections for which vancomycin is an optimal agent, specifically culture-proven methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative Staphylococcus (CoNS), and ampicillin-resistant Enterococcus infections, were defined as vancomycin requiring (VAN-req). Acute kidney injury (AKI) was defined as having a serum Creatinine of twice normal per age-related reference values.

Results

Of 304 identified SS cases, 8.9% had VAN-req infections. VAN was empirically given to 58.2% of cases (177); 86.4% ultimately did not have VAN-req infections. 9.2% of all SS cases had AKI at SS onset; this included 15.8% of patients (28) receiving VAN, of which only 1 (3.6%) had a VAN-req infection. History of a past MRSA infection, prolonged hospitalization, SNF residence, and CVL presence were found to be independent risk factors for a VAN-req infection (Table 1). VAN-req infections in patients lacking these four risk factors was 3.1% (4/130).

Conclusion

VAN was given empirically in the majority of pediatric SS cases, but culture-proven infections requiring the drug were infrequent, especially in patients without specific risk factors. The use of empiric VAN for SS should be guided by well-defined criteria, as the drug’s potential risks are likely to outweigh any benefit in most patients.

Disclosures

All authors: No reported disclosures.
Development of a 22/43 GHz-band quasi-optical perforated plate and dual-band observation system of the Nobeyama 45 m telescope
Authors: Okada Nozomi , Hashimoto Ikumi , Kimura Kimihiro , Manabe Takeshi , Tokuda Kazuki , Onishi Toshikazu , Ogawa Hideo , Imai Hiroshi , Minamidani Tetsuhiro
Published: October 2019

We have developed a system of simultaneous observations in the 22 and 43 GHz bands using the Nobeyama 45 m telescope, and are also working to add the 86 GHz band. Multi-frequency observations are realized by mounting perforated plates in the optics as dichroic frequency-selective devices. This paper presents the development of the perforated plate for the 22 and 43 GHz bands and the results of the commissioning observations with this plate on the Nobeyama 45 m telescope. The perforated plate is designed to be installed in the large telescope optics with a physical beam diameter as large as $50\:$cm for transmitting the higher frequency (43 GHz) band and for reflecting the lower frequency (22 GHz) band. The developed plate achieves an insertion loss of $0.22\:$dB (5%) at $43\:$GHz. The effects of the mounted plate on the systematic offsets and on the accuracy degradation of pointing were confirmed to be negligible. The differences in the main-beam/aperture efficiencies from those without the plate were confirmed to be within a few percent points. In addition, we successfully detected interferometry fringes in a very long baseline interferometry (VLBI) observation using the 45 m telescope and the VLBI Exploration of Radio Astrometry (VERA) 20 m telescopes, which confirmed that the dual-band observation system is operationally effective in both single-dish and VLBI observations.
Image-processing the topological charge density in the $\mathbb{C}P^{N-1}$ model
Authors: Abe Yuya , Fukushima Kenji , Hidaka Yoshimasa , Matsueda Hiroaki , Murase Koichi , Sasaki Shoichi
Published: October 2019

We study the topological charge density distribution using the 2D $\mathbb{C}P^{N-1}$ model. We numerically compute not only the topological susceptibility, which is a spatially global quantity, to probe the topological properties of the whole system, but also the topological charge correlator with finite momentum. We perform a Fourier power spectrum analysis for the topological charge density for various values of the inverse temperature $\beta$. We propose to utilize the Fourier entropy as a convenient measure to characterize spatial distribution patterns and demonstrate that the Fourier entropy exhibits nontrivial temperature dependence. We also consider the snapshot entropy defined with the singular value decomposition, which also turns out to behave nonmonotonically with the temperature. We give a possible interpretation suggested from the strong-coupling analysis.
Increased blood pressure during the suggested immobilization test in Restless Legs Syndrome
Authors: Rassu Anna Laura , Chenini Sofiène , Barateau Lucie , Lopez Regis , Evangelista Elisa , Guiraud Lily , Jaussent Isabelle , Dauvilliers Yves
Published: October 2019

Objective

To investigate the relationship between sensory discomfort/motor component and cardiovascular autonomic response by continuous beat-to-beat blood pressure monitoring (CBPM) during the suggested immobilization test (SIT) in patients with restless legs syndrome (RLS).

Methods

Thirty-two drug-free patients with primary RLS (10 men; mean age 60.29 ± 10.81 years) and 17 healthy controls (2 men; mean age 58.82 ± 11.86 years) underwent a 1-hour SIT starting at 8 pm with concomitant CBPM to measure the heart rate (HR) and systolic/diastolic blood pressure (SBP, DBP). In all subjects, the presence of sensory discomfort and motor component during the SIT (S-SIT+ and M-SIT+, respectively) was quantified. Mixed regression models were used to compare the SBP, DBP, and HR profiles during the SIT by taking into account the repeated measures (6 time periods of 10 minutes).

Results

In patients with S-SIT+ (n = 17), SBP (p < 0.0001), DBP (p = 0.0007), and HR (p = 0.03) increased during the SIT compared with other patients and controls. Seventeen patients had M-SIT+ (none among healthy controls). Classifying patients in 4 groups in function of the presence/absence of the SIT sensory and motor components revealed that SDB and DBP increased throughout the SIT in patients with S-SIT+, independently of the motor component (p < 0.0001 and p = 0.0008 for SBD; p < 0.0001 and p = 0.01 for DBP in the S-SIT+/M-SIT− and S-SIT+/M-SIT+ groups, respectively).

Conclusion

During the SIT, BP concomitantly increased only in patients with RLS and sensory discomfort, with or without motor component. This highlights the link between evening sensory RLS symptoms, autonomic activation, and potential long-term cardiovascular consequences.
Inhibition of human microsomal PGE2 synthase‐1 reduces seizure‐induced increases of P‐glycoprotein expression and activity at the blood‐brain barrier
Authors: Soldner Emma L. B. , Hartz Anika M. S. , Akanuma Shin‐Ichi , Pekcec Anton , Doods Henri , Kryscio Richard J. , Hosoya Ken‐Ichi , Bauer Björn
Published: October 2019

The cause of antiseizure drug (ASD) resistance in epilepsy is poorly understood. Here, we focus on the transporter P‐glycoprotein (P‐gp) that is partly responsible for limited ASD brain uptake, which is thought to contribute to ASD resistance. We previously demonstrated that cyclooxygenase‐2 (COX‐2) and the prostaglandin E receptor, prostanoid E receptor subtype 1, are involved in seizure‐mediated P‐gp up‐regulation. Thus, we hypothesized that inhibiting microsomal prostaglandin E2 (PGE2) synthase‐1 (mPGES‐1), the enzyme generating PGE2, prevents blood‐brain barrier P‐gp up‐regulation after status epilepticus (SE). To test our hypothesis, we exposed isolated brain capillaries to glutamate ex vivo and used a combined in vivo‐ex vivo approach by isolating brain capillaries from humanized mPGES‐1 mice to study P‐gp levels. We demonstrate that glutamate signaling through the NMDA receptor, cytosolic phospholipase A2, COX‐2, and mPGES‐1 increases P‐gp protein expression and transport activity levels. We show that mPGES‐1 is expressed in human, rat, and mouse brain capillaries. We show that BI1029539, an mPGES‐1 inhibitor, prevented up‐regulation of P‐gp expression and transport activity in capillaries exposed to glutamate and in capillaries from humanized mPGES‐1 mice after SE. Our data provide key signaling steps underlying seizure‐induced P‐gp up‐regulation and suggest that mPGES‐1 inhibitors could potentially prevent P‐gp up‐regulation in epilepsy.—Soldner, E. L. B., Hartz, A. M. S., Akanuma, S.‐I., Pekcec, A., Doods, H., Kryscio, R. J., Hosoya, K.‐I., Bauer, B. Inhibition of human microsomal PGE2 synthase‐1 reduces seizure‐induced increases of P‐glycoprotein expression and activity at the blood‐brain barrier. FASEB J. 33, 13966‐13981 (2019). www.fasebj.org
Keeping Residents Well: How Important Are Perceptions of Program Support and Psychological Safety to Resident Wellness?
Authors: Hylton Jordan , Karjane Nicole , Santen Sally , Rigby Fidelma , Appelbaum Nital
Published: October 2019

PURPOSE:

We aimed to test whether measures of resident well-being correlated with perceptions of program support and psychological safety.

BACKGROUND:

Trainee well-being is a crucial component of developing competent and skilled OB/GYN physicians. While there are several measures of well-being collected at the national-level, there is little insight in the role of individual programs to foster trainee well-being. Perceived organizational and psychological safety are two constructs that can help identify cultural aspects of the clinical learning environment that may relate to trainee well-being.

METHODS:

OBGYN residents in a training program were recruited to complete an IRB-approved survey through paper and electronic methods between May-June 2018. Measures included the Survey of Perceived Organizational Support (POS), Psychological Safety Scale (PS), Perceived Stress Scale (PSS), Wayne State Wellness Scale (RWS) and Physician Well-Being Index (PWBI); all demonstrate validity and reliability evidence to assess factors of well-being and cultural aspects of the training program.

Results:

20 OBGYN residents completed our survey. Results indicated a strong relationship between perceived organizational support and wellness (r=.62, P<.01 for RWS, r=.50, P<.05 for PWB)., suggesting greater perceptions of support relate to better wellness. Similarly, psychological safety also had a strong relationship with wellness (r=.56, p<.05 for RWS; r=-.72, p<.01 for PWB).

DISCUSSION:

Our findings suggest that there is a strong relationship between trainee wellness and the cultural measures of support and safety, especially between psychological safety and negative indicators of well-being (e.g., feeling burnt out from work, feelings of irritation). Further research should include interventions to improve perceptions of support and safety.
One Size Doesn’t Fit All for Wellness: Residents’ Perception of Wellness Programming
Authors: Winkel Abigail , Palmer James , Morgan Helen , Mahany Erica , Dow Margaret , Woodland Mark
Published: October 2019

PURPOSE:

To investigate which wellness interventions have the most meaning for a modern cohort of OB/GYN residents.

BACKGROUND:

The 2017 CREOG Resident Survey found significant associations between the learning environment and wellness. The primary analysis indicated that PGY-1's prioritized wellness, and that a sense of wellness decreased with each PGY level. In order to explore whether developmental stage influenced how wellness initiatives were perceived, we performed a secondary analysis of the survey to determine how residents at different PGY levels perceived wellness interventions.

METHODS:

A six-item survey on wellness was administered before the 2017 CREOG exam. IRB exemption was obtained. Participation was voluntary and anonymous, linked only to PGY level. A mixed-methods analysis of the data was performed. Descriptive statistics were analyzed with Microsoft Excel 2010. Mann-Whitney U tests were used to explore differences between PGY-levels. Thematic analysis of text responses was performed.

RESULTS:

Among the 5855 residents, 4,753 answered questions regarding wellness programming (81% RR). Significant differences existed between year of training and perceived effectiveness for several initiatives. PGY1 residents valued peer mentorship (p=0.003) and strategic napping (p<0.001) more than senior residents, while PGY3 residents emphasized faculty mentoring (p=.005). Regardless of training Level, residents prioritized the same three activities: wellness days to address personal needs, team-building retreats, and facilitated exercise programs.

DISCUSSION:

OBGYN residents perceive some wellness activities as valuable throughout training, while the importance of others may vary based on resident year. Most programs do not yet provide the wellness programs (retreats, facilitated exercise, personal time) that OBGYN residents identify as most effective.
Anorexia nervosa in adolescents
Authors: Peterson Kathleen , Fuller Rebecca
Published: October 2019

Anorexia nervosa (AN) is an eating disorder that is difficult to treat, and relapse is common. This article addresses management strategies and nursing interventions for adolescents diagnosed with AN.
Guidelines for difficult urethral catheterization in males
Authors: Warren Janelle , Ruckle Herbert C.
Published: October 2019

Urethral characterization can be difficult for patients and providers alike. This article describes an evidence-based protocol for difficult urethral catheter insertions in male patients.
Mentoring millennials for nursing leadership
Authors: Bittner Aubrey
Published: October 2019

As baby boomers continue to retire and millennials become the leading generation in the nursing workforce, nurse leaders must promote professional development and leadership opportunities for millennials moving forward. This article describes challenges and opportunities across the multigenerational nursing workforce along with suggestions on how to remove barriers and align with millennial nurses to provide meaningful mentorship and promote understanding and a positive work environment.
Differential expression and role of S100 proteins in chronic rhinosinusitis
Authors: Sumsion Jorgen S. , Pulsipher Abigail , Alt Jeremiah A.
Published: October 2019

Purpose of review

Immune system modulators have been under investigation to help elucidate the underlying pathophysiologies of chronic rhinosinusitis (CRS). Psoriasin (S100A7) and calgranulins (S100A8, S100A9, and S100A12) are S100 proteins that have been studied for their immune-mediating responses to pathogens within the context of CRS. This review highlights the expression patterns and proposed roles of S100 proteins in CRS with (CRSwNP) and without (CRSsNP) nasal polyps.

Recent findings

Elevated levels of S100A7 and S100A12 were measured in the sinonasal tissues of patients with CRSsNP compared with CRSwNP and controls. S100A12 expression in CRSsNP was significantly correlated to disease severity. Contrastingly, increased S100A8, S100A9, and S100A8/A9 levels were demonstrated in the nasal polyp tissues of patients with CRSwNP compared with those in inferior turbinate and uncinate tissues of patients with CRSsNP and controls.

The reported differential expression patterns and activities of psoriasin and calgranulins suggest that S100 proteins exert unique and concerted roles in mediating immunity in different subtypes of CRS. These studies will enable further investigations focused on understanding the immune-modulating mechanisms of S100 proteins in different inflammatory signaling pathways and disease phenotypes of CRS toward the pursuit of identifying new biomarkers and targets for improved outcomes.
The Development of New MD-Granting Medical Schools in the United States in the 21st Century
Authors: Whitcomb Michael E.
Published: October 2019

No new MD-granting medical schools were established during the 1980s and 1990s due to concerns that existed within the academic and policymaking communities that the United States was going to experience a major oversupply of physicians in the coming decades due to the increase that had occurred in medical school enrollment in the 1960s and 1970s. However, the results of studies conducted in the 1990s suggested that the country was actually going to experience a major shortage of physicians in the coming decades. As a result, new medical schools began to be established in the country after the turn of the 21st century. Since then, 29 new MD-granting medical schools have been established in the United States. This Invited Commentary examines some of the characteristics of the new schools and provides an overview of various factors that contributed to their development, including financial resources and geographic location.
Pain monitor: reality or fantasy in ambulatory patients
Authors: Farhang Borzoo , Mathews Donald M.
Published: October 2019

Purpose of review

In an unconscious patient, there can be significant challenges to monitoring nociception and proper dosing of analgesic medications. The traditional measures of intraoperative nociception have poor sensitivity and specificity with little predictive value in postoperative outcomes such as postoperative pain, opioid-induced side effects, length of stay or incidence of opioid use disorder. To date, several monitoring modalities are in development to establish objective measures of the balance between nociception and analgesia with the goal of guiding anesthesiologists and improve patient outcomes. In this review, some of the most promising monitoring modalities are discussed with the most recent findings.

Recent findings

Multiple modalities are beginning to demonstrate utility compared with traditional care. Most, but not all, of these studies show decreased intraoperative opioid use and some show lower pain scores and opioid requirements in the postanesthesia care unit.

Recent evidence points to promising efficacy for these monitoring modalities; however, this field is in its infancy. More investigation is required to demonstrate differences in outcome compared with traditional care, and these differences need to be of sufficient import to achieve widespread adoption.
Preoperative Vitamin D Concentration and Cardiac, Renal, and Infectious Morbidity after Noncardiac Surgery
Authors: Turan Alparslan , Artis Amanda S. , Hanline Cecelia , Saha Partha , Maheshwari Kamal , Kurz Andrea , Devereaux P. J. , Duceppe Emmanuelle , Patel Ameen , Tiboni Maria , Ruetzler Kurt , Pearse Rupert , Chan Matthew T. V. , Wu William K. K. , Srinathan Sadeesh , Garg Amit X. , Sapsford Robert , Sessler Daniel I.
Published: October 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery.

Methods

We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications.

Results

A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min-1 1.73 m-2 per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004).

Conclusions

Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.