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Background To reduce antibiotic prescribing, antimicrobial stewards must understand patient knowledge, attitudes, and perceptions (KAP) around antibiotics for URIs. Validated patient KAP surveys are scarce and for Veteran patients, nonexistent. We aimed to explore if published results of an exploratory factor analysis (EFA) of a KAP survey in emergency department (ED) patients and an online sample would approximate results in outpatient Veterans. Methods After cognitive testing in Veterans and healthcare providers, we omitted 13 of the 46 questions from the published KAP survey deemed confusing or with low factor loadings. We mailed the 33-item survey to Veterans seen for URI at 18 Veterans Affairs clinics from January 2018 to December 2019. We excluded Veterans not evaluated in-person, with documented dementia, or who died prior to study start. We excluded surveys with > 3 unanswered questions. We used principal component factor analysis (PCFA) with orthogonal varimax rotation (Fig. 1) to assess Veteran responses and Cronbach’s alpha to assess each factor’s internal consistency. We removed questions to reach alpha of >0.7 (Fig. 2). We repeated PCFA and compared results to published EFA factors and loadings for the ED patients and online sample. Results Of 1329 eligible Veterans invited, 474 (36%) returned the survey; 407 met inclusion criteria (Table 1). PCFA of Veterans’ responses yielded 7 Factors (Fig 2). Like ED patients and the online sample, Veteran responses about side effects clustered together. Veteran responses about “antibiotics help” and “antibiotics don’t hurt” clustered together like ED patients. They grouped separately in the online sample. Veteran responses about safety and efficacy (Factors 3 & 5) and knowledge about viruses and bacteria, (Factors 4 & 5) clustered separately (Fig. 2). For ED patients and the online sample, safety and efficacy and virus and bacteria responses clustered together, respectively (Fig. 1). Conclusion While Veterans did share some KAPs around antibiotics for URIs with ED patients and the online sample, this study shows they also have distinct views. Further testing in Veteran and non-Veteran populations should validate and assess reliability of this survey as an antimicrobial stewardship tool. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|Campbell Alliance/Syneos Health: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi-Pasteur: Advisor/Consultant Milner B. Staub, MD, MPH, Gilead: Stocks/Bonds|Johnson & Johnson: Stocks/Bonds.

INTRODUCTION: pH impedance testing is the most sensitive diagnostic test for detecting gastroesophageal reflux disease (GERD). The literature remains inconclusive on which preoperative pH impedance testing parameters are associated with an improvement in heartburn symptoms after anti-reflux surgery. The objective of this study was to evaluate which parameters on preoperative pH impedance testing were associated with improved GERD health-related quality of life (GERD-HRQL) following surgery. METHODS: Data from a single institution foregut database were used to identify patients with reflux symptoms who underwent anti-reflux surgery between 2014–2020. Acid and impedance parameters were extracted from preoperative pH impedance studies. GERD-HRQL was assessed pre- and postoperatively with a questionnaire that evaluated heartburn, dysphagia, and the impact of acid blocking medications on daily life. Patient characteristics, fundoplication type, and four pH impedance parameters were included in a multivariable linear regression model with improvement in GERD-HRQL as the outcome. RESULTS: We included 108 patients (59 Nissen and 49 Toupet fundoplications), with a median follow-up time of one year. GERD-HRQL scores improved from 22.4 (SD±10.1) preoperatively to 4.2 (±6.2) postoperatively. In multivariable analysis, a normal preoperative acid exposure time (p=0.01) and Toupet fundoplication (vs. Nissen; p=0.03) were independently associated with greater improvement in GERD-HRQL. CONCLUSIONS: Of the four pH impedance parameters that were investigated, a normal preoperative acid exposure time was associated with greater improvement in quality of life after anti-reflux surgery. Further investigation into the critical parameters on preoperative pH impedance testing using a multi-institutional cohort is warranted.

Nucleic acid nanoparticles (NANPs) have become powerful new platforms as therapeutic and diagnostic tools due to the innate biological ability of nucleic acids to identify target molecules or silence genes involved in disease pathways. However, the clinical application of NANPs has been limited by factors such as chemical instability, inefficient intracellular delivery, and the triggering of detrimental inflammatory responses following innate immune recognition of nucleic acids. Here, we have studied the effects of altering the chemical composition of a circumscribed panel of NANPs that share the same connectivity, shape, size, charge and sequences. We show that replacing RNA strands with either DNA or chemical analogs increases the enzymatic and thermodynamic stability of NANPs. Furthermore, we have found that such composition changes affect delivery efficiency and determine subcellular localization, effects that could permit the targeted delivery of NANP-based therapeutics and diagnostics. Importantly, we have determined that altering NANP composition can dictate the degree and mechanisms by which cell immune responses are initiated. While RNA NANPs trigger both TLR7 and RIG-I mediated cytokine and interferon production, DNA NANPs stimulate minimal immune activation. Importantly, incorporation of 2′F modifications abrogates RNA NANP activation of TLR7 but permits RIG-I dependent immune responses. Furthermore, 2′F modifications of DNA NANPs significantly enhances RIG-I mediated production of both proinflammatory cytokines and interferons. Collectively this indicates that off-target effects may be reduced and/or desirable immune responses evoked based upon NANPs modifications. Together, our studies show that NANP composition provides a simple way of controlling the immunostimulatory potential, and physicochemical and delivery characteristics, of such platforms.

There has been a surge of research on Home Children in the past several decades, as the phenomenon previously unknown to many came into the spotlight. However, much of the historical research has focused on either the psychological and physical impacts on the children at the hands of their new “families” (there were many reports of child abuse and neglect) or the ways they were saved from their poverty in Britain by being sent to the colonies. This article will put this existing historical research into conversation with theories of settler colonialism, considering Home Children as a tool of domestication for the social reproduction of Canadian white settler society, which was paired with the forced removal of Indigenous peoples from their lands. This analysis stems from and is intertwined with personal reflections on my own family history as a white settler woman descending from a Home Child to explore the gendered labour of social reproduction as a crucial pillar in creating and maintaining settler colonial Canada. Following Lorenzo Veracini’s argument that settler colonialism is a distinct structure that uses domestication as one of its key tenets and relies on its “regenerative capacity”, this paper will explore how British Home Children were a key component of settler colonialism in Canada and how this history has manifested in the current gendered, racialized, and classed politics of “settling”.

Background HIV+ donor (HIV D+) to HIV+ recipient (HIV R+) transplantation involves ethical considerations related to safety, consent, stigma, and privacy, which could be better understood through studying patients' actual experiences. Methods We interviewed kidney and liver transplant recipients enrolled in clinical trials evaluating HIV D+/R+ transplantation at 4 centers regarding their decision-making process, the informed consent process, and posttransplant experiences. Participants were interviewed at-transplant (≤3 wk after transplant), posttransplant (≥3 mo after transplant), or both time points. Interviews were analyzed thematically using constant comparison of inductive and deductive coding. Results We conducted 35 interviews with 22 recipients (15 at-transplant; 20 posttransplant; 13 both time points; 85% participation). Participants accepted HIV D+ organs because of perceived benefits and situational factors that increased their confidence in the trials and outweighed perceived clinical and social risks. Participants reported positive experiences with the consent process and the trial. Some described HIV-related stigma and emphasized the need for privacy; others believed HIV D+/R+ transplantation could help combat such stigma. There were some indications of possible therapeutic misestimation (overestimation of benefits or underestimation of risks of a study). Some participants believed that HIV+ transplant candidates were unable to receive HIV-noninfected donor organs. Conclusions Despite overall positive experiences, some ethical concerns remain that should be mitigated going forward. For instance, based on our findings, targeted education for HIV+ transplant candidates regarding available treatment options and for transplant teams regarding privacy and stigma concerns would be beneficial.

BackgroundAntibiotics are not recommended for treatment of acute uncomplicated bronchitis (AUB), but are often prescribed (85% of AUB visits within the Veterans Affairs nationally). This quality improvement project aimed to decrease antibiotic prescribing for AUB in community-based outpatient centres from 65% to MethodsFrom January to December 2018, community-based outpatient clinics’ 6 months’ average of prescribed antibiotics for AUB and upper respiratory infections was 63% (667 of 1054) and 64.6% (314 of 486) when reviewing the last 6 months. Seven plan–do–study–act (PDSA) cycles were implemented by an interprofessional antimicrobial stewardship team between January 2019 and March 2020. Balancing measures were a return patient phone call or visit within 4 weeks for the same complaint. Χ2 tests and statistical process control charts using Western Electric rules were used to analyse intervention data.ResultsThe AUB antibiotic prescribing rate decreased from 64.6% (314 of 486) in the 6 months prior to the intervention to 36.8% (154 of 418) in the final 6 months of the intervention. No change was seen in balancing measures. The largest reduction in antibiotic prescribing was seen after implementation of PDSA 6 in which 14 high prescribers were identified and targeted for individualised reviews of encounters of patients with AUB with an antimicrobial steward.ConclusionsOperational implementation of successful stewardship interventions is challenging and differs from the traditional implementation study environment. As a nascent outpatient stewardship programme with limited resources and no additional intervention funding, we successfully reduced antibiotic prescribing from 64.6% to 36.8%, a reduction of 43% from baseline. The most success was seen with targeted education of high prescribers.

Chemical injuries from household products cause significant morbidity and mortality annually in pediatric patients. We present a rare case of a 21-month-old male with significant esophageal and cutaneous chemical burns secondary to non-accidental trauma. Given the unique challenges associated with multiple burn types we describe this case and provide a current review of the literature on the management of these potentially devastating injuries.

The unknown immune stimulation by nucleic acid nanoparticles (NANPs) has become one of the major impediments to a broad spectrum of clinical developments of this novel technology. Having evolved to defend against bacterial and viral nucleic acids, mammalian cells have established patterns of recognition that are also the pathways through which NANPs can be processed. Explorations into the immune stimulation brought about by a vast diversity of known NANPs have shown that variations in design correlate with variations in immune response. Therefore, as the mechanisms of stimulation are further elucidated, these trends are now being taken into account in the design phase to allow for development of NANPs that are tailored for controlled immune activation or quiescence.

Background High-value healthcare focuses on improving healthcare to produce cost effective care, however limited information on the role of advanced practice registered nurses (APRNs) exists. Purpose This descriptive report describes APRN-led initiatives implemented as part of a national collaborative promoting the Choosing Wisely® campaign and high-value care measures. Method An APRN national collaborative focuses on developing and implementing high-value care initiatives. Monthly calls, podcasts, and a file sharing platform are used to facilitate the work of the national collaborative. Findings A total of 16 APRN teams from 14 states are participating and have implemented a number of initiatives to reduce unnecessary testing and treatments, promote appropriate antibiotic use, and promote optimal clinical practices such as mobility for hospitalized elderly patients, among others. Discussion A national collaborative has proven to be a successful way to engage APRN teams to focus on targeting high-value care and promoting evidence-based practices in clinical care.

Background: Antibiotics are not recommended but are often prescribed for upper respiratory-tract infections (URIs). Prescribers cite patient expectation as a driver of inappropriate antibiotic prescribing; prior literature has demonstrated higher satisfaction scores in patients who receive antibiotics compared to those who do not. We assessed whether veteran satisfaction at URI visits was associated with antibiotic receipt or with reported expectation for antibiotics. Methods: We surveyed veterans with documented URI encounters in the Veterans’ Affairs Tennessee Valley Healthcare System between January 1, 2018, and December 31, 2019. Patients not evaluated in person, with documented dementia, or who died prior to the study start date were excluded. Veterans were asked to recall their URI visit and to complete the Patient Safety Questionnaire (PSQ)-18 (Rand Corporation) and questions assessing antibiotic expectations. The PSQ-18, an 18-item survey that assesses patient satisfaction, uses a 5-point Likert scale (ie, strongly disagree, disagree, uncertain, agree, strongly agree), yielding a composite score of 18–90. Higher scores represent more satisfaction with care. Demographic and visit-specific information were extracted via chart review. We used multivariable linear regression to assess differences in composite PSQ-18 satisfaction scores between those who did and did not receive an antibiotic, adjusted for patient and visit characteristics, and to assess differences in satisfaction scores for those who did and did not report expecting antibiotics, adjusted for antibiotic receipt. Results: We identified 1,435 patients seen for URI at 17 sites. After exclusions, 1,343 veterans were eligible for chart abstraction. After excluding 42 responders who responded after study close or returned blank surveys, the final analytic cohort included 432 (32.2%) of 1,343 responders; 225 (52.1%) received an antibiotic and 207 (47.9%) did not. Mean total satisfaction for veterans who received an antibiotic was 67.8 (SD, ±9.4) compared to 66.7 (SD, ±9.7) for those who did not (Figure 1). Increased total satisfaction was not significantly associated with antibiotic receipt (0.65; 95% CI, −2.0 to 3.3). Most veterans (72.0%) disagreed that visit satisfaction depended on antibiotic receipt. However, only 30.8% reported that they would not expect an antibiotic for URI visits. A significant reduction in total satisfaction (−4.1; 95% CI, −6.3 to −1.9) was associated with expecting compared to not expecting an antibiotic. Conclusions: Our findings suggest that prescribing an antibiotic is not associated with increased veteran satisfaction for URI visits but is associated with expecting an antibiotic. Future work will evaluate methods to change veteran antibiotic expectations.Funding: NoDisclosures: None

Objective: To compare outcomes after bariatric surgery between Medicaid and non-Medicaid patients and assess whether differences in social determinants of health were associated with postoperative weight loss. Background: The literature remains mixed on weight loss outcomes and healthcare utilization for Medicaid patients after bariatric surgery. It is unclear if social determinants of health geocoded at the neighborhood level are associated with outcomes. Methods: Patients who underwent laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) from 2008 to 2017 and had ≥1 year of follow-up within a large health system were included. Baseline characteristics, 90-day and 1-year outcomes, and weight loss were compared between Medicaid and non-Medicaid patients. Area deprivation index (ADI), urbanicity, and walkability were analyzed at the neighborhood level. Median regression with percent total body weight (TBW) loss as the outcome was used to assess predictors of weight loss after surgery. Results: Six hundred forty-seven patients met study criteria (191 Medicaid and 456 non-Medicaid). Medicaid patients had a higher 90-day readmission rate compared to non-Medicaid patients (19.9% vs 12.3%, P < 0.016). Weight loss was similar between Medicaid and non-Medicaid patients (23.1% vs 21.9% TBW loss, respectively; P = 0.266) at a median follow-up of 3.1 years. In adjusted analyses, Medicaid status, ADI, urbanicity, and walkability were not associated with weight loss outcomes. Conclusions: Medicaid status and social determinants of health at the neighborhood level were not associated with weight loss outcomes after bariatric surgery. These findings suggest that if Medicaid patients are appropriately selected for bariatric surgery, they can achieve equivalent outcomes as non-Medicaid patients., Mini-abstract: The relationship among Medicaid status, social determinants of health, and bariatric surgery outcomes is unclear. Using electronic health record data and social determinant variables geocoded at the neighborhood level, we found that Medicaid status, socioeconomic deprivation, household location (rural vs urban), and neighborhood walkability were not associated with weight loss outcomes after bariatric surgery. However, Medicaid patients had higher readmission rates within 90 days of surgery. Supplemental Digital Content is available in the text.

Anti-TAG-72 monoclonal antibodies target the tumor-associated glycoprotein (TAG)-72 in various solid tumors. This study evaluated the use of anti-TAG-72 monoclonal antibodies, both murine CC49 and humanized CC49 (HuCC49deltaCH2), for near-infrared fluorescent (NIR) tumor imaging in colorectal cancer xenograft models. The murine CC49 and HuCC49deltaCH2 were conjugated with Cy7 monofunctional N-hydroxysuccinimide ester (Cy7-NHS). Both in vitro and in vivo anti-TAG-72 antibody binding studies were performed. The in vitro study utilized the human colon adenocarcinoma cell line LS174T that was incubated with Cy7, antibody-Cy7 conjugates, or excessive murine CC49 followed by the antibody-Cy7 conjugates and was imaged by fluorescence microscopy. The in vivo study utilized xenograft mice, bearing LS174T subcutaneous tumor implants, that received tail vein injections of Cy7, murine CC49-Cy7, HuCC49deltaCH2-Cy7, or nonspecific IgG-Cy7 and were imaged by the Xenogen IVIS 100 system from 15 min to 288 h. The biodistribution of the fluorescence labeled antibodies was determined by imaging the dissected tissues. The in vitro study revealed that the antibody-Cy7 conjugates bound to LS174T cells and were blocked by excessive murine CC49. The in vivo study demonstrated that murine CC49 achieved a tumor/blood ratio of 15 at 96 h postinjection. In comparison, HuCC49deltaCH2-Cy7 cleared much faster than murine CC49-Cy7 from the xenograft mice, and HuCC49deltaCH2-Cy7 achieved a tumor/blood ratio of 12 at 18 h postinjection. In contrast, Cy7 and Cy7 labeled nonspecific IgG resulted in no demonstrable tumor accumulation. When mice were injected with excessive unlabeled murine CC49 at 6 h before the injection of murine CC49-Cy7 or HuCC49deltaCH2-Cy7, both the intensity and retention time of the fluorescence from the tumor were reduced. In summary, the Cy7 labeled murine CC49 and HuCC49deltaCH2 demonstrate tumor-targeting capabilities in living colorectal cancer xenograft mice and provide an alternative modality for tumor imaging.

In the past few years, the study of therapeutic RNA nanotechnology has expanded tremendously to encompass a large group of interdisciplinary sciences. It is now evident that rationally designed programmable RNA nanostructures offer unique advantages in addressing contemporary therapeutic challenges such as distinguishing target cell types and ameliorating disease. However, to maximize the therapeutic benefit of these nanostructures, it is essential to understand the immunostimulatory aptitude of such tools and identify potential complications. This paper presents a set of 16 nanoparticle platforms that are highly configurable. These novel nucleic acid based polygonal platforms are programmed for controllable self-assembly from RNA and/or DNA strands via canonical Watson-Crick interactions. It is demonstrated that the immunostimulatory properties of these particular designs can be tuned to elicit the desired immune response or lack thereof. To advance the current understanding of the nanoparticle properties that contribute to the observed immunomodulatory activity and establish corresponding designing principles, quantitative structure-activity relationship modeling is conducted. The results demonstrate that molecular weight, together with melting temperature and half-life, strongly predicts the observed immunomodulatory activity. This framework provides the fundamental guidelines necessary for the development of a new library of nanoparticles with predictable immunomodulatory activity.

18 F-fluorodeoxyglucose positron emission tomography–computed tomography is integral to the staging of lung cancer. We describe the combined use of diagnostic preoperative 18 F-fluorodeoxyglucose positron emission tomography–computed tomography, intraoperative 18 F-fluorodeoxyglucose handheld gamma probe detection, and immediate postoperative 18 F-fluorodeoxyglucose positron emission tomography–computed tomography patient and specimen imaging for improved staging and determination of adequacy of mediastinal lymph node dissection.

A letter to the editor is presented in response to the article "Real Men Don't: Constructions of Masculinity and Inadvertent Harm in Public Health Interventions" by P.J. Fleming, J.G. Lee, and S.L. Dworkin which appears in a 2014 issue of the journal.

Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaCH2), radiolabeled with iodine-124 (124I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging. Methods HuCC49deltaCH2 was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of 18F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection. Results At approximately 1 hour after i.v. injection, 124I-HuCC49deltaCH2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, 18F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder. Conclusions On microPET imaging, 124I-HuCC49deltaCH2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while 18F-FDG failed to demonstrate this. The antigen-directed and cancer-specific 124I-radiolabled anti-TAG-72 monoclonal antibody conjugate, 124I-HuCC49deltaCH2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.