bluuebunny/crossref_metadata_2025_split huggingface dataset:
2758. Identifying Populations at High-Risk for Influenza-Related Hospitalization: A Real-World Analysis of Commercially Insured Population in the United States
Authors: Burudpakdee Chakkarin , Near Aimee , Tse Jenny , Young-Xu Yinong , Connolly Lynn , Reyes Carolina M 
Published: October 2019

Abstract

Background
The disease burden of seasonal influenza (flu) is high and contributes to morbidity, mortality and healthcare utilization. While only 1–2% of flu cases are hospitalized, these events are costly. The objective of this study was to describe and quantify risk factors for flu hospitalization.

Methods
Patients with 1 flu diagnosis (Dx) over 4 seasons (October 1, 2014–May 31, 2018) in IQVIA’s Real-World Data Adjudicated Claims – US database were selected into the study; the earliest flu Dx was the index date. Patients were required to have ≥12 months continuous enrollment in their health plan before index (baseline), ≥30 days after index, and either a record of a flu test ± 14 days of index or a flu Dx in the primary position. Comorbidities during a fixed 12-month baseline period were categorized by AHRQ and CDC definitions. The study outcome of interest, flu-related hospitalization during the 30-day follow-up period, was defined as hospitalization with Dx of flu or a pre-defined flu-related complication in any position. A logistic regression model assessed the odds of flu-related hospitalization, adjusting for age, sex, region, payer, season of index Dx, evidence of flu vaccination, and comorbidities.

Results
More than 1.6 million medically-attended flu cases were identified, of which 18,509 (1%) had a hospitalization. 40% of patients were < 18 years of age, 47% were male, and 28%, 15%, 24%, and 33% were identified in the 2014–2017 flu seasons, respectively. More hospitalized patients were ages 50+ compared with non-hospitalized patients (57% vs. 20%) and 44% of hospitalized patients had 4 or more AHRQ/CDC comorbidities vs. 8% of non-hospitalized patients. In adjusted analyses, older age (65+ vs. 5–17; OR = 9.4, 95% CI 8.8–10.1) and leukemia/lymphoma/metastatic cancer (OR = 3.2, 95% CI = 2.9–3.5) were key drivers of hospitalization (Figure 1).

Conclusion
The risk of flu-related hospitalization is high for elderly populations and those with certain underlying co-morbidities among all age groups. While these findings reflect the burden of medically-attended flu in a younger, commercially insured population, additional research is needed to address the flu burden in high-risk populations.

Disclosures
All authors: No reported disclosures.
2759. Immunogenicity of Inactivated Influenza Vaccines Given Early vs. Late After Pediatric Allogeneic Hematopoietic Cell Transplantation
Authors: Schuster Jennifer E , Schuster Jennifer E , Speaker Andrew , Hamdan Lubna , Batarseh Einas , Stewart Laura S , Dulek Daniel , Kitko Carrie L , Munoz Flor M , Munoz Flor M , Bocchini Claire , Danziger-Isakov Lara , Grimley Michael , Goyal Rakesh , Coffin Susan E , Freedman Jason L , Englund Janet A , Carpenter Paul A , Ardura Monica I , Auletta Jeffrey , Wattier Rachel , Truong Kenny , Maron Gabriela , Allison Kim J , Halasa Natasha B 
Published: October 2019

Abstract

Background
Pediatric hematopoietic cell transplant (HCT) recipients often fail to have robust responses to influenza (flu) vaccine. We conducted a blinded phase II trial comparing high-dose (HD) trivalent inactivated vaccine (TIV) vs. standard dose (SD) quadrivalent inactivated vaccine (QIV).

Methods
Children 3–17 years old and 3–35 months post-allogeneic HCT were enrolled at 9 centers and randomized to either 2 doses of HD-TIV or SD-QIV during the 2016–2017 flu season. We compared immune responses by hemagglutination inhibition (HAI) from children 3–11 (early) vs. 12–35 (late) months (m) post-HCT to 3 common flu vaccine antigens, irrespective of vaccine type. HAI responses were evaluated at baseline (visit 1), 1 m post dose 1 (visit 2) and dose 2 (visit 3), and 7 m post dose 2 (visit 4). Geometric mean titers (GMT) were adjusted for baseline log-titer values.

Results
Thirty-one children, median age 11 (7–15) years, were enrolled; 17 (55%) were immunized early and 14 (45%) late. Over 50% of patients had a potentially seroprotective (≥1:40) HAI titer at baseline, with no significant difference post-vaccination between early and late subjects. Table 1 compares early vs late subjects with HAI seroconversion (4-fold HAI titer rise). Post dose 1, late subjects, compared with early, had higher rates of seroconversion to all influenza strains. Post dose 2, early subjects, compared with late, had increased seroconversion. Late subjects had higher GMTs for H1N1 post dose 1 and 2, H3N2 after dose 1, and strain B/VIC post dose 1 and 2 (Figure 1). Although immunogenicity waned throughout flu season, higher seroconversion rates and GMT to H3N2 and strain B/VIC were retained in late subjects.

Conclusion
Compared with subjects in early post-HCT group, late post-HCT subjects had better flu vaccine immune responses as noted by higher GMT and HAI seroconversion. However, 2 doses seemed more beneficial in the early post-HCT group. Future analyses are underway, including comparing immunogenicity of HD vs. SD flu vaccine.

Disclosures
Jennifer E. Schuster, MD, Satchel Health: Shareholder Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.
2768. Does Social Media Contribute to Knowledge About Vaccine Safety?
Authors: Zheteyeva Yenlik , Hannan Jennifer , Goss Mary Ann , Straus Walter 
Published: October 2019

Abstract

Background
Social media is frequently used to share medical information. Current European regulatory guidance for the pharmaceutical industry calls for reporting valid adverse events (AE) derived from social media as well as consideration of non-valid AEs. This guidance is followed when our company utilizes social media related to any company products and interests. Here we evaluate its application to vaccines.

Methods
Posts collected from all screened social media sources (company owned, or company reviewed) were examined (August 1, 2017–February 28, 2019) to identify safety-related information pertaining to any of its 14 licensed vaccines. Posts were classified as valid cases (i.e., containing information about company product, AE, and identifiable reporter), non-valid cases (i.e., company product, AE, but missing an identifiable reporter), or not relevant (no safety-related information; not further analyzed). Valid cases were added to the company’s safety database; non-valid cases were reviewed for trends requiring further analysis. Both, valid and non-valid cases, were analyzed as part of routine safety surveillance

Results
Among 69,682 vaccine-related posts reviewed, 285 (0.4%) were valid; 11,464 (16.5%) were non-valid; 47,966 (83.1%) were not relevant. Most non-valid cases concerned the company’s 4-valent (8,934 [78%]) or 9-valent (1,420 [12%]) human papillomavirus vaccines, followed by its measles-mumps-rubella (336 [2.9%]), pneumococcal (282 [2.5%]), and herpes zoster (246 [2.1%]) vaccines. Review of data from selected temporal spikes in posts demonstrated that they were usually attributable to increased reposts of an original post or to personal views, rather than containing incremental factual new safety data.

Conclusion
Fewer than 1% of posts from relevant social media sources contained sufficient information to be considered valid cases. No new safety signals were identified for any of the vaccines from social media cases (valid or non-valid). Among posts containing safety information, the nature of this information tends to be redundant or sentimental, precluding meaningful safety analyses.

Disclosures
All authors: No reported disclosures.
2779. Efficacy of the Adjuvanted Recombinant Zoster Vaccine According to Sex, Geographic Region, and Geographic Ancestry/Ethnicity: A Post-hoc Analysis
Authors: Willer David O , Wascotte Valentine , Kim Joon Hyung , Zahaf Toufik , Talarico Carla , Gorfinkel Iris , Gervais Pierre , Pharm Pharm, L , Cunningham Anthony L , Oostvogels Lidia , Colindres Romulo , Schuind Anne 
Published: October 2019

Abstract

Background
The risk of herpes zoster (HZ) has been reported to vary by sex and ethnicity. In 2 large-scale clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) demonstrated high vaccine efficacy (VE) against HZ and post-herpetic neuralgia (PHN). We present a post-hoc analysis of RZV efficacy against HZ and PHN in the ZOE-50/70 population stratified by sex, geographic region and geographic ancestry/ethnicity.

Methods
The ZOE-50 and ZOE-70 studies were phase III, observer-blind, placebo-controlled trials conducted across 5 geographic regions. Adults ≥ 50 years of age (YOA; ZOE-50) and ≥ 70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Here, VE against HZ by sub-population was estimated from the ZOE-50 population (≥ 50 YOA) and the pooled ZOE-50/70 population (pooled ≥ 70 YOA), and VE against PHN by sub-population was evaluated in the pooled ≥ 70 YOA.

Results
VE was evaluated in 7,340 RZV and 7,413 placebo recipients ≥ 50 YOA (mean age: 62.3 [RZV], 62.2 [placebo] YOA) and 8,250 RZV and 8,346 placebo recipients in pooled ≥ 70 YOA (mean age: 75.5 [RZV, placebo] YOA). VE against HZ and PHN was similar for women and men in the ≥ 50 YOA and pooled ≥ 70 YOA (Tables 1 and 2). Point estimates for VE against HZ by geographic region ranged from 95.7% to 97.2% in ≥ 50 YOA and from 87.3% to 95.1% in pooled ≥ 70 YOA (Table 1). Point estimates for VE against PHN by geographic region ranged from 86.8% to 100% in pooled ≥ 70 YOA. VE was similar across geographic ancestry groups in pooled ≥ 70 YOA: VE point estimates against HZ ranged from 89.6% to 100% and VE against PHN ranged from 87.5% to 100% (Tables 1 and 2). VE against HZ was 88.1% and against PHN was 65.9% in Hispanic participants in pooled ≥ 70 YOA (Tables 1 and 2).

Conclusion
Acknowledging the limitations including the post-hoc character of these analyses and the small number of participants and cases available, our data suggest that RZV is efficacious against HZ and PHN irrespective of sex, geographic region, geographic ancestry, and ethnicity.
Funding: GlaxoSmithKline Biologicals SA.

Disclosures
All authors: No reported disclosures.
2781. Statistical Modeling to Predict Maternal RSV Vaccine Efficacy from Neutralizing Titers
Authors: Cai Bing , Chen Yili , Agosti Yasmeen , Swanson Kena , Schmoele-Thoma Beate , Jansen Kathrin U , Gruber William C , Koury Kenneth , Dormitzer Philip R 
Published: October 2019

Abstract

Background
In the United States, respiratory syncytial virus (RSV) is the leading cause of respiratory-related hospitalization in infants. The well-studied efficacy of the prophylactic monoclonal antibody, palivizumab, at preventing RSV disease in the highest risk infants provides proof of mechanism that serum neutralizing antibody protects against RSV. The expense and burden of monthly antibody injections limit the utility of palivizumab, leaving a large unmet medical need. Maternal immunization, with transplacental transfer of antibodies to the fetus, is an alternative, highly practical approach to protect many more infants.

Methods
Levels of protection by known palivizumab serum concentrations provide a basis for predicting maternal RSV vaccine efficacy in infants based on serum neutralizing antibody titers elicited in vaccine clinical trials, using statistical modeling to compensate for differences between palivizumab prophylaxis and maternal immunization. The model adjusts for the dependency of maternal vaccine responses on pre-immunization RSV neutralizing titers, exponential decay of maternal antibodies in infants, and exponentially decreasing airway resistance (reducing RSV disease risk) as infants grow.

Results
The rates of severe RSV disease by age projected from the model match the pattern of US infant hospitalization for RSV, with a peak at 1.5 months of age. The model relates vaccine-elicited increases in maternal RSV neutralizing titers to predicted reductions in severe RSV disease in infants from 0 to 6 months of age.

Conclusion
Statistical modeling of maternal RSV vaccine efficacy based on elicited RSV neutralizing titers provides a rational basis for decision-making during RSV vaccine development.

Disclosures
All authors: No reported disclosures.
2783. Expansion of Monocytic Myeloid-Derived Suppressor Cells in Infants with Severe Respiratory Syncytial Virus (RSV) Infection
Authors: Bedoya Santiago Acero , Ye Fang , Best Victoria , Ramilo Octavio , Ramilo Octavio , Mejias Asuncion 
Published: October 2019

Abstract

Background
RSV remains a leading cause for hospitalization of infants. The mechanisms associated with the ability of RSV to suppress the induction of an adequate immune response are not well understood and represent a challenge for vaccine development. Myeloid-derived-suppressor cells (MDSCs) have been shown to suppress CD8+ T cells in patients with malignancies. These immature myeloid cells are divided into three groups: granulocytic, monocytic, and undifferentiated. Of those, monocytic MDSCs (M-MDSCs) are considered to be key regulators of inflammatory responses during acute infections. Their potential role in the immunopathogenesis of RSV infection in infants is yet to be defined.

Methods
Single-center, prospective cohort study in previously healthy infants hospitalized with severe RSV lower respiratory tract infection (LRTI) and age-matched healthy controls (HC). Nasopharyngeal swabs for RSV detection and blood samples for cell immunophenotyping were analyzed at enrollment (D1), 1-month (D30), and 6-months (D180) follow-up visits. Disease severity was assessed using a clinical disease severity score (CDSS), duration of supplemental O2, and duration of hospitalization.

Results
We enrolled 39 infants with RSV LRTI (median [IQR] age: 3.3 [1.5–5.2] months) and 5 HC (5.9 [4.5–7.2] months). Infants with RSV infection demonstrated an expansion of M-MDSCs during the acute infection (D1) that resolved to numbers comparable to those in HC at follow-up visits (Figure 1A). In addition, numbers of CD8+ T cells were significantly reduced during the acute infection (D1) in RSV-infected infants, but also returned to the HC baseline on D30 and D180 (Figure 1B). Finally, the increase in M-MDSCs numbers and decrease in CD8+ T-cell numbers were associated with worse clinical outcomes as defined by duration of supplemental oxygen (>1 day), hospitalization (>48 hours), and clinical disease severity score (CDSS, > 9) (Figure 2).

Conclusion
These findings suggest that an expansion of M-MDSCs may play a role in T-cell suppression in children with severe RSV disease. As new vaccines are being developed, it is critical to elucidate the immune suppressive mechanisms associated with RSV infection.

Disclosures
Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.
2787. Respiratory Syncytial Virus in Elderly Adults
Authors: Mykietiuk Analía , Obed Mora , Cooke Bettina , Fernanda; Alzogaray Maria , Romandetta Agustin , Pablo Balbuena Juan , Galeano Lucia , Chaparro Gustavo , Baumeister Elsa 
Published: October 2019

Abstract

Background
The role of respiratory viruses other than influenza in acute respiratory tract infections (ARTI) among elderly adults has probably been underestimated. Recent advances in molecular diagnosis have made the rapid identification of RSV infection possible.The aim of our study was to assess the role of RSV in patients older than 65 years.

Methods
Prospective observational study (April 2018–February 2019) conducted in a 137-bed institution in Buenos Aires, Argentina. All consecutive elderly patients (>65 years) admitted with ARTI were included. Clinical and laboratory parameters as well as nasopharyngeal swab for respiratory viruses were obtained. Blood cultures and sputum collection, were analyzed. Viral detection was performed according to CDC real-time RT–PCR assay. All patients underwent clinical follow-up during hospitalization and up to 30 days after discharge.

Results
A total of 124 patients were recruited (mean age 82 years; range: 65–98) 58% female. Clinical diagnosis at admission were: community-acquired pneumonia 90 (72%), COPD exacerbation 11 (9%), acute bronchitis 10 (8%), healthcare-associated pneumonia 8 (7%) influenza like síndrome 5 (4%). Blood cultures were obtained in 92 patients: 4 positives for Streptococcus pneumoniae, 3 E. coli, 2 SAMS, 1 Klebsiella pneumoniae. Sputum was obtained in 20 patients, none were positive.The viral results of the124 samples were: RSV 13 (10.4%), Influenza B 9 (7.2%), Influenza A 8 (6.4%).Regarding RSV positive patients, the mean age was 87 years and 69% were female. 30 % had history of heart failure and 30 % had history of COPD. Clinical diagnosis on admission were: CAP 10 (77%), COPD exacerbation 2 (15%) and bronchitis 1 (8%). Non productive cough was present in 46% and bronchospasm in 85%. Mean time of hospitalization was 9 days (R: 4–16) and fever duration 1 day (R: 0–2). The median duration of antibiotic treatment was 9.5 days (R: 4 to 15) No viral nor bacterial coinfections were observed. No early mortality was registered, global mortality was 23% (3 patients). Death was clinically related to RSV infection.

Conclusion
This study suggest that RSV is a relevant respiratory pathogen in the elderly population, with significant associated morbidity and mortality rates. Current treatment is limited to supportive care and prevention to standard infection control practices. A new approach is needed to improve RSV infection management.

Disclosures
All authors: No reported disclosures.
2794. Testing and Treatment in Patients Hospitalized with Suspected Influenza Pneumonia
Authors: Deshpande Abhishek , Klompas Michael , Bartley Patricia , Yu Pei-Chun , Haessler Sarah , Zilberberg Marya , Imrey Peter , Rothberg Michael 
Published: October 2019

Abstract

Background
Influenza is a leading cause of community-acquired pneumonia (CAP). Little is known about the effect of influenza testing on antimicrobial treatment among adult patients hospitalized with CAP. We quantified prevalence of testing and impact of positivity on treatment with antibacterials, antivirals, and outcomes.

Methods
We included adults admitted with pneumonia in 2010–2015 to 179 US hospitals contributing to the Premier database. Patients had CAP if radiographic evidence of pneumonia and antimicrobial treatment were present on day 1. We assessed influenza testing and compared antimicrobial utilization and outcomes of patients who tested positive vs negative vs not tested. Using mixed logistic regression and gamma generalized linear mixed models, we assessed the impact of influenza testing on inpatient mortality, length of stay (LOS) and cost.

Results
Among 166,273 patients with CAP, 38,665 (23.2%) were tested for influenza; 11.5% of these tested positive. The influenza testing rate increased from 15.4% in 2010/7–2011/6 to 35.6% in 2014/7–2015/6, ranging from 28.8% during flu season (October–May) to 8.2% in other months. Positive tests were more common during flu season (12.2% vs. 2.8%, P < 0.001). Patients tested for influenza were younger (66.6 vs. 70.3 years), less likely admitted from SNF (5.4% vs. 7.9%), with fewer comorbidities (2.9 vs. 3.3). Of patients tested for influenza, positive patients were younger (66.3 vs. 68.8 years), less likely admitted from SNF (5.2% vs. 6.8%), with more comorbidities (2.9 vs. 2.7) (all comparisons P < 0.001). Patients testing positive more likely received antivirals, were slightly less likely to receive antibacterials (Figure 1), but received shorter antibacterial courses than negative patients (5.3 vs 6.4 days, P < 0.001). Influenza tests were associated with reduced odds of in-hospital mortality compared with no testing (adjusted OR 0.71, 95% CI 0.63–0.81) and positive vs. negative tests with reduced costs (0.95, 0.92–0.99) and LOS (0.97, 0.94–0.99) (Figure 2).

Conclusion
In a large US inpatient sample hospitalized for pneumonia, only 23.2% of the patients were tested for influenza, but testing varied widely by hospital. A positive influenza test was associated with antiviral treatment but had minimal impact on antibiotic prescribing.

Disclosures
All authors: No reported disclosures.
2796. The Impact of Syndromic Molecular Point-of-Care Testing for Respiratory Viruses on Antibiotic Use in Adults Presenting to Hospital with Exacerbation of Airways Disease: Further Analysis From a Randomized Controlled Trial
Authors: Clark Tristan William , Mills Samuel , Brendish Nathan 
Published: October 2019

Abstract

Background
The ResPOC study demonstrated that syndromic molecular point-of-care testing (POCT) for respiratory viruses was associated with earlier discontinuation of unnecessary antibiotics. Subgroup analysis suggests this occurs predominantly in patients with exacerbation of airways disease. Molecular POCT use is becoming widespread but there is a lack of evidence to inform the choice between multiplex syndromic panels vs. uniplex tests for influenza.

Methods
We evaluated patients with exacerbation of asthma or COPD who were treated with antibiotics. The duration of antibiotics and proportion with early discontinuation were compared between patients testing positive for viruses by POCT (FilmArray Respiratory Panel) those testing negative by POCT and controls. Patients testing positive for viruses by POCT were compared according to virus types detected. Survival curves were generated for duration of antibiotics and compared using the log-rank test.

Results
There were 118 patient with exacerbation of airways disease in the POCT group who received antibiotics and 111 in the controls. In the POCT group 49/118 (42%) patients tested positive for viruses. Of those testing positive for viruses by POCT 17/49 (35%) had early discontinuation of antibiotics vs. 9/81 (13%) in those testing negative and 7/111 (6%) in controls, P < 0.0001. Survival curve analysis showed a reduced time to antibiotic discontinuation in those testing positive for viruses, P = 0.034. Of those positive for viruses by POCT 20% were positive for influenza, 43% for rhinovirus and 37% for other viruses combined. The proportion with early discontinuation of antibiotics was not different between the virus types, P = 0.53.

Conclusion
Syndromic molecular POCT for viruses in adults with exacerbation of airways disease leads to early discontinuation in those positive for viruses. As most viruses detected were non-influenza viruses and there was no difference in antibiotic use between virus types, syndromic molecular POCT for respiratory viruses should be favored over uniplex POCT for influenza.

Disclosures
All authors: No reported disclosures.