Objectives:We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED). Methods:We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020. Results:We collected data from 3128 subjects; 2196 in the derivation cohort and 932 in the validation cohort. Medical comorbidities, multifocal opacities or pleural effusion on chest radiography, older age, elevated respiratory rate, hypoxia, elevated blood urea nitrogen, blood glucose, blood lactate, and red blood cell distribution width were factors associated with intubation or death. We developed the Predicting Intubation in seasonal Influenza Patients diagnosed in the ED (PIIPED) risk-stratification tool from these factors. The PIIPED tool predicted intubation or death with an area under the receiver operating characteristic curve (AUC) of 0.899 in the derivation cohort and 0.895 in the validation cohort. A version of the tool including only factors available at ED triage, before laboratory or radiographic evaluation, exhibited AUC of 0.852 in the derivation cohort and 0.823 in the validation cohort. Conclusion:Clinical findings during an ED visit predict severe outcomes in patients with seasonal influenza. The PIIPED risk stratification tool shows promise but requires prospective validation.

Purpose: To support and explore medical students’ professional identity formation1 as a physician through experiential learning in authentic clinical environments, which occurs during their preclinical years, allowing for earlier association of preclinical knowledge to patient-specific contexts and earlier engagement with threshold concepts2 essential to becoming a physician. Approach: Innovation: Throughout phase 1 of Washington University School of Medicine’s (WUSM’s) new Gateway Curriculum, preclinical students complete three, 3-week clinical immersions. There are 3 types of immersions—ambulatory/emergency department, procedural/surgical, and inpatient, across a variety of specialties. Incorporating experiential learning theory,3 students perform clinical activities like those of clerkships—taking medical histories, performing physical exams, presenting patients, calling consults, writing notes, and participating in the operating room, as well as activities focused on course objectives such as incorporation within an interprofessional team, talking with patients about their lived experiences, and discussing the impact of health systems on patients. Furthermore, activity cards have students record clinical practice activities related to course objectives. Assessment of students within each immersion occurs via direct observation and longitudinal clinical performance assessments, evidence-based medicine critical appraisals, and analytic writing assignments. These writing assignments require students to demonstrate understanding of rotation objectives based on their lived clinical experiences. Writing prompts for these assignments ask students to discuss course content related to objectives, such as interprofessional care teams, systems-based care, social determinants of health, and personal learning goals developed through reflective use of feedback. Evaluation: Students evaluate immersions through satisfaction ratings and open-text comments on end-of-immersion questionnaires. WUSM’s Program Evaluation/Continuous Quality Improvement Unit (PECQI) summarized ratings and categorized open-text comments on the questionnaires. A separate team of 3 evaluators, who were not part of PECQI and not involved in planning or implementing the immersions, analyzed a sample of the analytic writing assignments from all 3 types of immersions using conventional content analysis.4 Outcomes: The first cohort in the Gateway Curriculum includes 105 students, all of whom completed all 3 immersions and associated assignments. Qualitative analysis of a sample of data, obtained at completion of the students’ third immersion, shows that students consistently describe their role as a liminal state from a passive observer—self-identified as a student trait—to an increasingly active care provider—a trait associated with the physician’s role. Students comment on discomfort and growth of this transitional stage, noticing, for example, the benefits and flaws of health care systems as they interact with social determinants of health, the interprofessional care team, patients, and their patients’ families. Students identify the value of communication, partnering with patients, and learning from interprofessional team members. In aspirational statements, students begin to self-identify threshold concepts central to their future identity as a physician such as patient-centeredness, the importance of equitable care, comfort with ambiguity, and need for lifelong learning. Quantitative data show that students feel that critical elements of immersions occur and that students self-identified “working in interprofessional teams” and “opportunities to practice clinical care” as well-executed aspects of the immersions. The analytic writing assignment prompts provide a lens for professional development, encouraging the student to reflect on their transition from student to physician in multiple contexts. Qualitative data from the written assignments show that these intentionally designed clinical immersions coupled with longitudinal, guided self-reflection expose medical students to key threshold concepts of physician professional identity formation. Significance: As a direct result of their participation within clinical interprofessional teams, combined with the directed learning of clinical immersions, preclinical students begin to frame their remaining preclinical activities through the lens of their identity as a future physician. Therefore, students enter their clerkship years having already begun their development of a professional identity as a physician.

In 2020, the authors published work examining disparities in clerkship grading and found students who identify as White were more likely to receive honors grades compared with students from races/ethnicities traditionally underrepresented in medicine. Through a quality improvement approach, the authors identified the following 6 areas where improvements could mitigate grading disparities and, therefore, put processes in place to: ensure equitable access to examination preparation resources, change student assessment, develop medical student curriculum interventions, improve the learning environment, change house staff and faculty recruitment and retention practices, and provide ongoing program evaluation and continuous quality improvement processes to monitor for success. While the authors cannot yet be sure that they have achieved their goal of promoting equity in grading, they believe this evidence-based, multipronged intervention is a clear step in the right direction and encourage other schools to consider a similar approach to tackling this critically important problem at their own institutions.

The earth is rapidly warming, driven by increasing atmospheric carbon dioxide and other gases that result primarily from fossil fuel combustion. In addition to causing arctic ice melting and extreme weather events, climatologic factors are linked strongly to the transmission of many infectious diseases. Changes in the prevalence of infectious diseases not only reflect the impacts of temperature, humidity, and other weather-related phenomena on pathogens, vectors, and animal hosts but are also part of a complex of social and environmental factors that will be affected by climate change, including land use, migration, and vector control. Vector- and waterborne diseases and coccidioidomycosis are all likely to be affected by a warming planet; there is also potential for climate-driven impacts on emerging infectious diseases and antimicrobial resistance. Additional resources for surveillance and public health activities are urgently needed, as well as systematic education of clinicians on the health impacts of climate change.

AbstractBackgroundThere are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.MethodsAdult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment.ResultsA total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012).ConclusionsThe primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation.Clinical Trials Registration. NCT01644877.

The COVID-19 pandemic disrupted medical education worldwide, leading medical students to organize response initiatives. This paper summarizes the Washington University Medical Student COVID-19 Response (WUMS-CR) and shares lessons to guide future initiatives. We used a three-principle framework of community needs assessment, faculty mentorship, and partnership with pre-existing organizations to address needs in St. Louis, including contact tracing and childcare. In total, over 12,000 h were volunteered across 15+ projects. Overall, student response initiatives should use appropriate frameworks to guide projects and should capitalize on volunteer participation, speed and flexibility, and the diversity of student interests and skills for maximal impact.

In 2018, in response to a news story featuring the Icahn School of Medicine's decision to eliminate its chapter of Alpha Omega Alpha (AOA) due to perceived racial inequities, students at Washington University School of Medicine in St. Louis (WUSM) brought similar concerns to leadership. WUSM leadership evaluated whether students' race, ethnicity, and gender were associated with their receipt of honors in the 6 core clerkships, key determinants of AOA selection. In preliminary analysis of the school's data, statistically significant racial and ethnic disparities were associated with receipt of honors in each clerkship. Leaders shared these findings with the WUSM community along with a clear message that such discrepancies are unacceptable to the school. An effort to further analyze what lay behind the findings as well as to identify steps to resolve the problem was launched. Using a quality improvement framework, data from focus groups and student surveys were analyzed and 2 overarching themes emerged. Students perceived that both assessment and the learning environment impacted racial/ethnic disparities in clerkship grades. In multivariable logistic regression models, shelf exam scores (a part of student assessment) were found to be associated with receipt of honors in each clerkship; in some (but not all) clerkships, shelf exam scores attenuated the effect of race/ethnicity on receipt of honors, so that when the shelf scores were added to the model, the race/ethnicity effect was no longer significant. This case study describes WUSM's process to understand and address bias in clerkship grading and AOA nomination so that other medical schools might benefit from what has been learned.

Traditional replicating smallpox vaccines are associated with serious safety concerns in the general population and are contraindicated in immunocompromised individuals. However, this very population remains at greatest risk for severe complications following viral infections, making vaccine prevention particularly relevant. MVA-BN was developed as a non-replicating smallpox vaccine that is potentially safer for people who are immunocompromised. In this phase II trial, 3 MVA-BN dosing regimens were evaluated for safety, tolerability, and immunogenicity in persons with HIV (PWH) who had a history of AIDS. Following randomization, 87 participants who were predominately male and African American received either 2 standard doses on weeks 0 and 4 in the standard dose (SD) group (N = 27), 2 double-standard doses on the same schedule in the double dose (DD) group (N = 29), or 3 standard doses on weeks 0, 4 and 12 in the booster dose (BD) group (N = 31). No safety concerns were identified, and injection site pain was the most commonly reported solicited adverse event (AE) in all groups (66.7%), with no meaningful differences between groups. The incidence of severe (Grade 3) AEs was low across groups and no serious AEs or AEs of special interest considered related to study vaccine were reported. Doubling the standard MVA-BN dose had no significant effect on induction of neutralizing antibodies, with 100% seroconversion and comparable GMTs at week 6 in the SD and DD groups (78.9 and 100.3, respectively). A booster dose significantly increased peak neutralizing titers in the BD group (GMT: 281.1), which remained elevated at 12 months (GMT: 45.3) compared to the SD (GMT: 6.2) and DD (GMT: 10.6) groups. However, based on the immune response previously reported for healthy participants, a third dose (booster) does not appear necessary, even for immunocompromised participants. Clinical Trial Registry Number: NCT02038881.

Abstract Background Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective. Methods This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults aged ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule. Results A single dose increased the levels of neutralizing (plaque reduction neutralization test to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (interferon-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T-cell responses (up to 2.8-fold from preboost levels). No drug-related serious adverse events were reported. Conclusions MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings. Clinical Trials Registration NCT02873286

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s Accepted for Presentation CHI 2020 1. CHI Workshop, April, 25, 2020, online presentation (Steven Rick), Cognitive Bias in Patient-Provider Communication: Sensing and Design to Reduce Health Disparities: Steven R. Rick (UC San Diego), Erin Beneteau (University of Washington) Regina Casanova-Perez (University of Washington), Cezanne Lane (University of Washington) Colleen Emmenegger (UC San Diego), Janice Sabin (University of Washington), Wanda Pratt (University of Washington), Andrea Hartzler (University of Washington) Nadir Weibel (UC San Diego) Manuscripts In Progress, data collection complete, data analysis in progress: 1. Tjia, J., Sabin, JA, Others TBD, A Study to Improve Communication between Clinicians and Patients of Color and Lower SES Populations: Methods and Challenges of COmmuNity-engaged SimULation Training for Blood Pressure Control (CONSULT-BP) Trial (Sabin, senior author) 2. Sabin, JA, Guenther, Ordelias, Patterson, Gujral, Morales, Frogner, Implicit Bias in the Clinical and Learning Environment: Impact of a Course for Clinical Educator Faculty. 3. Sabin, JA, Guenther, Ordelias, Patterson, Gujral, Morales, Frogner. Recruiting a National Sample of Healthcare Providers Using a Targeted Approach and Publicly Available Information 4. Sabin, JA, Guenther, Ordelias, Patterson, Gujral, Morales, Frogner. Clinicians' Strategies to Mitigate the Impact Of Implicit Bias on Teaching and Patient Care Following a Brief Course on Implicit Bias In The Clinical And Learning Environment Book in Progress Sabin, J.A., & Pitruzzello, P. R., VINCENZA 1917: A Story of Love of God and Love of Country is a narrative nonfiction book that recounts the early life and emigration of our grandmother, Vincenza Pitruzzello, born in Mellili, Sicily in 1898. The overarching message of this book is a celebration of America's rich history of immigration. f. Abstracts: 1. Sabin J. A., November, 2004, Racial And Ethnic Health Care Disparities: A Unified Theory Of Unequal Treatment In Health Care, oral presentation, Paper presented at the 132nd annual meeting of the American Public Health Association, Washington DC. 2. Sabin, J.A., June, 2005, oral presentation, Measuring Implicit Racial Bias: Using The Implicit Association Test In Health Services Research, Paper presented at the meeting of Curriculum Vitae Janice A. Sabin August 2020 Society for Epidemiological Research (SER) and Canadian Society for Epidemiology and Biostatistics (CSEB) combined annual meeting, Toronto, Canada. And published in American Journal of Epidemiology, 161 (Suppl.) S92. 3. Sabin, J. A., Greenwald, A. G., & Rivara, F. P., December, 2005, Measuring Health Care Provider Implicit Racial Bias: Using The Implicit Association Test In Health Care Research. Poster session presented at the 133rd annual meeting of the American Public Health Association, Philadelphia, PA. Awarded First Prize, Spirit of 1848 Caucus. 4. Sabin, J. A., Rivara, F. P., Greenwald, A. G., November, 2007, oral presentation, Physician Racial Bias and Medical Care, Oral presentation at 135th annual meeting of the American Public Health Association, Washington DC. 5. Sabin, J. A., Nosek, B. A., Greenwald, A. G., Rivara, F.P., October 28, 2008, oral presentation, Comparing Physician Implicit And Explicit Attitudes About Race By Gender, Race And Ethnicity. 136th annual meeting of the American Public Health Association, Medical Care section, San Diego, CA. 6. Murray, L, Sabin, J. A., Ferguson, G., Tsosie, U., Sawchuk, G., Bowen, D., Buchwald, B., March 18-20, 2009, poster presentation, Alaska Workplace Solutions, Alaska Native Health Research Conference, Anchorage, AK. 7. Sabin, J.A., VanSchaik, E., April 20, 2009, oral presentation, 2009 WGEA WGSA WMAS WAAHP Conference, Healthcare Disparities: An E-Learning Course for Providers, AAMC Western Regional Conference, Santa Fe, NM. 8. Sabin, J. A., VanSchaik, E., Lynch, E., Stoner, S., June, 2010, poster presentation, Does awareness of unconscious associations enhance learning about healthcare disparities? Society for Epidemiological Research (SER) annual meeting, Seattle, WA. and published in American Journal of Epidemiology, 171(Suppl), S1–S157. 9. Sabin, J.A., VanSchaik, E., June, 2011, poster presentation, Academy Health Annual Meeting, Applying the Science of Unconscious Bias to Health Care Disparities Research, Seattle, WA. 10. Sabin, J.A., Greenwald, A., February 4, 2011, poster presentation. Pediatricians’ Implicit Attitudes and Stereotypes about Race and Pain Management Recommendations for African American and White Patients, National Institutes of Health, Science of Research on Discrimination and Health Summit, Bethesda, Maryland. 11. Sabin, J.A., Oliver, N., & Blair, I. November 15, 2011, invited panel presentation, North American Primary Care Research Group (NAPRC), Annual Meeting, National Ethnic/Racial Bias and Health Disparities: How do we measure it? How do we eliminate it? November 1216, Banff Alberta, Canada. 12. Sabin, J.A., Kieckhefer, G., Phipps, W., Ratcliffe, M., Salldin, C., Redding, G., November 12, 2012, poster presentation, A Successful Model of Interprofessional Clinical and Leadership Graduate Education for the Disciplines of Medicine, Nursing, Nutrition, and Social Work, 2012 AAMC annual meeting, San Francisco, CA. Curriculum Vitae Janice A. Sabin August 2020 13. Van Schaik, E., Sabin, J. A., December, 2012, poster presentation, NIH 2012 Summit on the Science of Eliminating Health Disparities, Healthcare Disparities: Patients and Providers an e-learning course, December 17, 2012, Washington DC. 14. Sabin, J.A., & Pitruzzello, P. P., The Vincenza Project: 2014, Italian American Studies Association (IASA) 37th annual meeting, Conference Theme: Italians Without Borders: Transnational Italian (American) Experience, University of Toronto, Toronto, Canada. (submitted abstract for oral presentation 3/1/2014, accepted for oral presentation 7/1/14 for October 17-19, 2014, Toronto) 15. Sabin, J. A., Moore, K., Noonan, C., Lallemand, O., Buchwald, D., 2014, The influence of continuing education on Indian Health Service primary care providers' self-rated weight management approaches for American Indian children. Association of American Medical Colleges, Medical Education annual meeting, Chicago, IL. (submitted abstract May, 2014, accepted for poster presentation 6/24/2014 for November 6-7, 2014, Chicago) LOCAL AND REGIONAL INVITATIONAL LECTURES: 1. Sabin, JA. May 2005, invited presentation, Harborview Injury Prevention and Research Center, University of Washington, Seattle, WA, Primary Care Utilization and Detection of Emotional Distress Following Adolescent Traumatic Injury: Identifying an Unmet Need, Seattle, WA. 2. Sabin, J.A., April, 2006, oral presentation, Investigating Health Care Provider Implicit and Explicit Racial Bias and Implications for Medical Care, Institute on Inequality and Social Structure, Spring Colloquium, School of Social Work, University of Washington, Seattle, WA. 3. Sabin, J.A., May, 2006, oral presentation, University of Washington Summit on Health Disparities: Diversity and Social Determinants of Health, Investigating Implicit and Explicit Racial Bias: Implications for Medical Care, Seattle, WA. 4. Sabin, J.A., May, 2006, oral presentation, Health Care Disparities: Health Care Provider Biases, University of Washington Medical Center, Human Resources Department, Seattle, WA. 5. Sabin, J.A., September, 2006, oral presentation, Seattle Children’s Hospital, Seattle, WA. Center for Diversity Committee, September 20, 2006, Health Care Provider Implicit And Explicit Racial Bias And Medical Care, Seattle, WA. 6. Sabin, JA. May 2006, invited speaker, University of Washington, Summit on Health Disparities: Diversity and Social Determinants of Health, Investigating Implicit and Explicit Racial Bias: Implications for Medical Care, Seattle, WA. 7. Sabin, JA. May 2006, oral presentation, University of Washington Medical Center, Human Resources Department, Health Care Disparities: Health Care Provider Biases, Seattle, WA. 8. Sabin, JA. September 20, 2006, oral presentation, Children’s Hospital and Regional Medical Center, Center for Diversity Committee, Health Care Provider Implicit And Explicit Racial Bias And Medical Care, Seattle, WA. Curriculum Vitae Janice A. Sabin August 2020 9. Sabin, JA., February 2008, oral presentation and invited guest speaker, Social Work (Soc W 598), Psychology (PSYCH 550) or Health Services (HSERV 590 D). Integrative Seminar on Health Disparities: The Case of Tobacco (master’s, doctoral level students), Seattle, WA. 10. Sabin, JA. January 23, 2008, invited speaker, (SSW 506) Social Welfare Research and Evaluation. From Clinical Practice to Research Design and Implications of Findings: A Mechanism to Explain Discrimination in Health Care, Seattle, WA. 11. Sabin, JA. April 15, 2008, guest speaker, Dept of Pediatric Dentistry University of Washington, Unconscious Bias and its Influence on Provider-Patient Communication, Seattle, WA. 12. Sabin, J.A., October, 2008, oral presentation, The Collaborative Care Conference, Network of Family Medicine Residency Programs, University of Washington, Teachable Moments When Medicine and Culture Collide: What Effective Teaching Tools Will You Need, Seattle, WA. Spring Colloquium, School of Social Work, University of Washington, Investigating Health Care Provider Implicit and Explicit Racial Bias and Implications for Medical Care, Seattle, WA. 13. Sabin, JA. October 14, 2009, presentation, Pediatric Pulmonary Center (PPC) Training Grant Core Seminar: Racial and Ethnic Disparities in Health Care: A Multidisciplinary Perspective, Seattle, WA. 14. Sabin, JA. August 2009, invited speaker, UW Bothell, BIS312, Social Psychology, Racial and Ethnic Disparities in Health Care: A Multidisciplinary Perspective, Seattle, WA. 15. Sabin, JA. June 2009, invited speaker, A. G. Greenwald, Psychology Graduate Seminar, Department of Psychology, University of Washington, Using th

Background PIV infections are an important cause of morbidity and mortality in HCT recipients. DAS181, a sialidase fusion protein, has demonstrated activity in pre-clinical and clinical studies. Methods Adult immunocompromised patients (IC), including HCT recipients, diagnosed with PIV LRTI on chest imaging and required SO ≥ 2L/min were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5mL/day) or matching placebo for up to 10 consecutive days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45. An exploratory end point of proportion to return to room air (RTRA) was analyzed. Results Out of the 110 patients randomized, 64 HCT recipients received study drug (43 DAS181 and 21 placebo). Median age was 53 years (range, 19-77), half were male (50%), white (84%), and had received an allogeneic HCT (86%). A post-hoc analysis of the HCT recipients on SO showed that day 45 CSS was achieved by 46.5% of DAS181-treated patients compared to 33.3% of placebo (p = 0.23). In addition, when compared to placebo, HCT recipients on SO who received DAS181 within 1 year from transplant were more likely to achieve CSS at day 45 (48.4% vs. 12.5%; p = 0.071), were more likely to RTRA at day 28 and day 45 (53.3% vs. 12.5%; p = 0.04 and 60% vs. 25%; p = 0.086, respectively), more likely to be discharged from the hospital by day 45 (64.5% vs. 12.5%; p = 0.011), and had a trend for lower mortality at day 45 (25.8% vs. 62.5%, p = 0.064). The rate of adverse events was similar in both treatment groups. Conclusion DAS181 was well tolerated and a post-hoc analysis in HCT recipients with PIV LRTI on SO within 1 year of transplant, DAS181 was effective (RTRA) and showed a trend towards lower mortality by day 45. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned.

Abstract Background BK virus-associated hemorrhagic cystitis (BK-HC) is a common and often serious complication of hematopoietic cell transplantation (HCT). Studies have suggested a higher incidence of BK-HC in patients receiving haploidentical (haplo) HCTs compared with those receiving matched unrelated donor (MUD) transplants. Methods We retrospectively identified all adult patients receiving HCT from MUD or haplo donors at Washington University School of Medicine between January 1, 2011 and January 1, 2016. Via informatics queries, we obtained the results of every urine BK test performed on these patients. Patients with BK viruria were then evaluated for BK-HC and graded according to established criteria. The last day of follow-up was April 31, 2017. Results 503 MUDs and 140 haplos were identified for inclusion in the study. Haplo patients were significantly more likely to be nonwhite (21% vs. 5%, P < 0.001) and were younger (median age: 51.5 vs. 55, P = 0.01). Conditioning regimens were also significantly different; haplos were less likely to receive myeloablative conditioning (44% vs. 57%, P < 0.001) and busulfan-based conditioning (13% vs. 39%, P < 0.001), but were more likely to receive total body irradiation-based conditioning (83% vs. 26%, P < 0.001). Haplos were also more likely to have undergone previous allogeneic HCT (26% vs. 6%, P < 0.001). The cumulative incidence of both BK viruria and BK-HC were significantly higher in haplos (both P < 0.001). This was observed at 100 days, 180 and 365 days (Table 1). Conclusion We found a significantly higher incidence of both BK viruria and BK-HC in patients receiving haplo HCT compared MUD HCT. Significant demographic and clinical imbalances exist between our two cohorts and attribution of increased risk for BK-HC to donor type vs. other factors should be further explored. Disclosures All authors: No reported disclosures.

There is limited knowledge on the yield of performing multiplex nucleic acid testing (NAT) on multiple lower respiratory tract specimens from a single patient with a single instance of infection. We evaluated the performance characteristics of multiplex NAT assays performed concurrently on bronchoalveolar lavage (BAL) and bronchial wash (BW) specimens to detect respiratory pathogens. A retrospective study of admitted patients from March 2013 through December 2016 was performed. Individual performance characteristics of BAL and BW specimens were compared to positive results from either set of specimens. Only contemporaneous BAL and BW specimens (received by the laboratory within 4 h of each other) were included. The final cohort included 170 patients, with 184 contemporaneous BAL and BW specimens submitted for multiplex NAT (median age, 58 years; 62% male). Of the patients with positive NAT results, 38 of 40 BW specimens tested positive (overall percent agreement with combined testing, 98.9%; 95% confidence interval [CI], 95.5 to 98.9%), and 34 of 40 BAL specimens tested positive (overall percent agreement with combined testing, 96.7%; 95% CI, 93.0 to 96.7%). Assays performed on BW specimens identified 4 additional specimens and had a higher positive percent agreement (95.0%) with combined testing results compared to those performed on BAL specimens (85.0%). There was exact concordance in 174 specimens (94.6%; negative and positive for respiratory pathogens, 144 and 34 specimens, respectively). We observed high concordance (95%) between multiplex NAT results from contemporaneous BAL and BW specimens. Performance characteristics of BW specimen testing were equivalent to those of BAL specimen testing. The benefit of performing additional testing should be carefully considered against the potential complications and health care costs.

BACKGROUND:Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.METHODS:The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637.RESULTS:Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment.CONCLUSIONS:The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA.TRIAL REGISTRATION:ClinicalTrials.gov NCT01144637.

Background:Influenza leads to significant morbidity and mortality in patients with cancer. Patients with cancer receiving chemotherapy may not mount an adequate immune response to the vaccine. We performed this pilot study to evaluate the immunogenicity of influenza vaccination in patients with cancer receiving chemotherapy.Materials and Methods:During the 2011 to 2012 influenza season, patients undergoing chemotherapy for solid tumors were given trivalent inactivated influenza vaccine either on the day of chemotherapy (schedule A) or a week before chemotherapy (schedule B) by a single 0.5 mL injection in the deltoid muscle region. This was not a randomized trial. Hemagglutination inhibition assays were performed on blood samples from these patients taken at baseline, and 4 weeks postvaccination. Seroconversion rate (>4-fold increase in titers) and seroprotection rates (postvaccination titers of >1:40) were calculated for each vaccine component: influenza A (H1N1), A (H3N2) and B.Results:A total of 18 patients received influenza vaccination as part of this pilot study. Of these, 8 patients received the vaccine on schedule A and 10 patients received the vaccine on schedule B. Geometric mean titers against each strain significantly improved after vaccination for both groups, as measured by signed rank test. Seroconversion to at least 1 strain was observed in 75% of patients on schedule A, and 70% of patients vaccinated on schedule B. Seroprotection to at least 1 strain was observed in 100% of patients in the schedule A group, and 60% of patients vaccinated on schedule B. Seroconversion and seroprotection rates against the 3 influenza strains were not significantly different between the 2 groups.Conclusions:Patients with nonhematological malignancies who are receiving chemotherapy mount an immune response to influenza vaccination. Timing of influenza vaccination in relation to chemotherapy does not seem to matter.

Abstract Background PIV infections are an important cause of morbidity and mortality in IC patients. DAS181, a sialidase fusion protein, has demonstrated activity in preclinical and clinical studies. Methods Adult IC patients diagnosed with PIV LRTI on chest imaging and required SO ≥ 2 L/minute were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5 mL/day) or matching placebo for up to 10 days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45. Results From 2014 to 2016, 110 patients were randomized and received study drug (74 DAS181 and 36 placebo). Median age was 57 years (range, 18–85). The majority were hematopoietic cell transplant (HCT) recipients (74), followed by hematological malignancy/solid tumor patients on chemotherapy (29), and lung transplant recipients (7). Day 45 CSS was achieved by 39.2% of DAS181-treated patients compared with 31.4% of placebo (P = 0.29), while the proportion among non-MV patients was 45.0% vs. 31.0% (difference −14.0%, P = 0.15), respectively. Time to CSS in the non-MV stratum was shorter in DAS181-treated patients (figure). Median change in nasopharyngeal PIV viral load by Day 10 and median hospitalization days were −1.44 vs. −0.68 log10 (P = 0.51) and 13.5 vs. 21 days (P = 0.10) for DAS181 and placebo, respectively. Mean absolute increase from baseline FEV1% predicted was 16.82 for DAS181 vs. 2.02 for placebo (P = 0.001). Post-hoc analysis on the probability to return to room air (RTRA) suggested that DAS181 reduced SO need in the non-MV stratum after Day 21 (P = 0.09). HCT recipients within 360 days from transplant had a 40.8% treatment effect on RTRA at Day 28 (P = 0.04) and 36.7% on mortality at Day 45 when compared with placebo (P = 0.06). The rate of adverse events was similar in both treatment groups. Day 45 all-cause mortality was comparable in both groups (32.4% DAS181 vs. 31.4% placebo). Conclusion DAS181 was well tolerated and showed a signal for clinical efficacy in IC patients with PIV LRTI. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned. Disclosures R. F. Chemaly, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research grant. R. Moss, Ansun Biopharma: Employee, Salary. F. M. Marty, Ansun Biopharma: Investigator, Research grant. C. R. Wolfe, Ansun Biopharma: Investigator, Research grant. S. J. Lawrence, Ansun Biopharma: Investigator, Research grant. S. Dadwal, Ansun Biopharma: Investigator, Research grant. R. Soave, Ansun Biopharma: Investigator, Research grant. J. Hwang, Ansun Biopharma: Employee, Salary. S. Hawley, Ansun Biopharma: Employee, Salary. R. Routh, Ansun Biopharma: Employee, Salary. J. Ho, Ansun Biopharma: Employee, Salary. G. Wang, Ansun Biopharma: Employee, Salary. N. Chang, Ansun Biopharma: Employee, Salary. M. Boeckh, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research support.

Background: Community associated pneumonia (CAP) is one the most common causes of hospital admissions, exceeding more than one million per year in the United States, contributing to 3.4% of inpatient mortality. Our objective was to compare 30-day mortality using therapies recommended for treatment of CAP. Methods: A multicenter retrospective analysis from four different hospitals was assessed from 2008 to 2013. The data was obtained from electronic medical records which included more than 70,000 patients. CAP patients were identified using discharge diagnostic codes during the years 2008-2013, as well as receiving therapy with ceftriaxone and azithromycin or a respiratory fluoroquinolone. Demographic data, antibiotic therapy, and Charlson comorbidity score was obtained to compare the study groups. Results: A total of 21,800 patients met the inclusion criteria for CAP. 1,740 patients were excluded as they received both beta-lactams and fluoroquinolones. The study included 20,600 patients. 11,201 patients (55.84%) received ceftriaxone with azithromycin, and 8,859 (44.16%) received fluoroquinolone therapy. The mortality rate for patients who received fluoroquinolone therapy was lower compared to the patients who received ceftriaxone plus azithromycin (3.56% vs 6.71%, p-value <0.001). Conclusions: Our study showed statistically significant lower 30-day mortality using fluoroquinolone therapy compared to ceftriaxone plus azithromycin for treatment of CAP. Prospective blinded randomized control trials would be needed to support this evidence. DOI: 10.18297/jri/vol2/iss2/4 Received Date: July 20, 2018 Accepted Date: August 9, 2018 Website: https://www.louisville.edu/jri Copyright: ©2018 the author(s). This is an open access article distributed under the terms of the Creative Commons AttributionNoDerivatives 4.0 International License (CC BY-ND 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Affiliations: 1Department of Medicine, Division of Infectious Diseases, Henry Ford Hospital, Detroit MI 2Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 3Washington University, St. Louis, MO 4Baylor Scott & White Health, Dallas, TX 5Wayne State University School of Medicine, Detroit, MI *Correspondence To: Gina Maki, DO Work Address: Department of Internal Medicine Henry Ford Hospital 2799 West Grand Boulevard Detroit, Michigan, USA. Work Email: gmaki1@hfhs.org Work Phone: 313-916-3623 19 © ULJRI 2018 Vol 2, (2) ORIGINAL RESEARCH hospital length of stay, readmission status, and mortality within 30 days was collected from each of the four hospitals’ electronic medical records (EMR). Information was obtained from each participating centers’ EMR which was then entered into a single database. This database included approximately 70,000 patients. Data was de-identified and coded using explicit data specifications and uploaded into one large database. The study protocol was approved by the institutional review board (IRB) at each participating institution. Teleconferences, enrollments reports, and data audits were conducted between the four study sites to ensure uniform data collection. All hospitalized patients in these hospitals between January 1, 2008 and December 30, 2012 with a discharge diagnosis of pneumonia were identified. Patients were included in the present study if: 1) They were aged ≥18 years; 2) They had received either ceftriaxone plus azithromycin, levofloxacin, or moxifloxacin for the duration of the hospitalization with no other antibiotics administered. Exclusion criteria included: 1) Patients who received other antimicrobial agents; 2) Patients with diagnosis of pneumonia with no information on therapy; 3) Patients who received both therapies. The primary outcome of the study was 30-day all-cause mortality. In hospital mortality was used as a marker for 30-day mortality, as our database was unable to assess 30-day mortality. The patients’ severity of comorbidities was assessed using Charlson comorbidity index. Statistical Methods Univariate statistical analysis was used to test the association of demographic and clinical characteristics with all-cause discharge mortality. Categorical variables were analyzed using the Chi-squared test or Fisher’s exact test. Continuous variables were analyzed using an unpaired t-test. All variables with a p-value < 0.05 in the univariate analysis were included into the multivariate logistic regression. The stepwise selection method was performed to generate the final model (P≤0.05 required for variable entry, P≤0.10 required for variable removal). All p-values were two-sided. Analyses were performed by using SAS 9.4.

Abstract Background Invasive fungal infections (IFI) remain a serious complication in hematopoietic stem cell transplantation (HSCT) patients and are associated with increased costs, morbidity, and mortality. Posaconazole (PCZ) and voriconazole (VCZ) are frequently utilized as antifungal prophylaxis in this population. To date, no direct comparison between PCZ and VCZ exists for the prevention of IFI in adult HSCT patients. Methods A retrospective cohort analysis of HSCT patients aged ≥18 years who received ≥28 continuous days of primary (PPPx) or secondary (SPPx) antifungal prophylaxis with either VCZ or PCZ between February 26, 2003 and September 30, 2015 at Barnes-Jewish Hospital was conducted. Patients who received PPPx or SPPx with both VCZ and PCZ were analyzed following intention to treat of the initial agent received. Patients who received both PPPx and SPPx were included once for both PPPx and SPPx. The primary outcome of interest was development of possible, probable, or proven IFI as defined by EORTC/MSG guidelines. In the SPPx patients, development of IFI was confirmed as a distinct event from primary IFI based on manual chart review and radiographic evidence. Results Overall, there were 472 patients included; 402 in the VCZ group and 70 in the PCZ group. At baseline, patients in the PCZ group had more graft vs. host disease (GVHD) prior to prophylaxis (27.1% vs. 16.7%, P = 0.04) and were more likely to be on SPPx (60% vs. 41%, P < 0.01). There were 22 and 1 IFI events in the VCZ and PCZ groups, respectively, which corresponded to a crude incidence rate of 0.345 and 0.077 per 1000 person-days of prophylaxis. Figure 1 displays the Cox proportional hazard model which was completed in the backwards stepwise method accounting for gender, transplant type, GVHD prior to prophylaxis, disease remission, and PPPx or SPPX. The hazard ratio for development of IFI while on prophylaxis between VCZ and PCZ was 5.22 (95% CI: 0.69–39.4; P = 0.11) after controlling for PPPx or SPPx. Conclusion There was not a significant difference between rates of IFI in HSCT patients who received antifungal prophylaxis with VCZ compared with PCZ. Our data trends towards favoring PCZ but is limited by low rates of IFI. Larger, prospective analyses are necessary to confirm our findings. Disclosures W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Astellas: Grant Investigator, Research grant

Healthcare-associated pneumonia (HCAP) is a common and potentially life threatening illness. Pneumonia is one of the most common causes of healthcare associated infections. The purpose of our study was to investigate in a large multicenter cohort over a several year period, the association of specific organisms with patient mortality in HCAP patients. This is a retrospective multicenter analysis of patients over 18 years of age hospitalized with HCAP over a 6-year period from 2008 to 2013 from 4 large healthcare institutions. Patients were identified by electronic medical record review. HCAP was defined by inclusion of patients with a discharge diagnosis of pneumonia by ICD-9 code plus associated antibiotic use in the initial 24 hours. Patients were considered to have HCAP if initial antimicrobial use included one of the following: cefepime, doripenem, meropenem, imipenem, or piperacillin-tazobactam, in combination with vancomycin or linezolid. There were 16084 patients. Staphylococcus aureus was the most common organism isolated in 368 patients and had 15.0% mortality at 30 days. Pseudomonas aeruginosa was isolated in 359 patients and had 24.2% mortality at 30 days. Acinetobacter baumannii was isolated in 200 patients, and accounted for 34.0% mortality. Escherichia coli was isolated in 89 patients with 24.7% mortality. Klebsiella pneumoniae was isolated in 99 patients with 27.3% mortality. Commensal bacteria were isolated or positive cultures with no speciation occurred in 5214 of patients with 22.8% mortality at 30 days. The remaining patients did not have organisms identified in the blood or sputum. Most patients with HCAP did not have an organism isolated. Mortality rate in these patients was generally similar to patients in whom an organism was identified except for S. aureus and A. baumannii. In patients from whom organisms were identified, S. aureus was most common and E. coli was the least common. Thirty-day mortality was highest in A. baumannii, and lowest with S. aureus. The lower mortality in patients with S. aureus is potentially related to early effective therapy. The high percentage of deaths due to A. baumannii is potentially related to both severe underlying disease and multidrug resistance limiting therapy options. M. Zervos, Merck: Investigator, Research grant; Genentech: Investigator, Research grant; Cempra: Investigator, Research grant; Pfizer: Investigator, Research grant