bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics (PK) and Safety of Intravenous (IV) Brincidofovir (BCV) in Healthy Adult Subjects
Authors: Wire Mary Beth , Morrison Marion , Anderson Maggie , Arumugham Thangam , Dunn John , Naderer Odin 
Published: October 2017

Abstract

Background
BCV is a lipid conjugate nucleotide that has shown rapid viral clearance in patients with adenovirus infection and improved survival in animal models of smallpox. In preclinical studies in rats, IV BCV dosed twice weekly for up to 29 days was not associated with gastrointestinal (GI), hematopoietic, hepatic, or renal toxicity. This study evaluated the safety and PK of IV BCV in healthy subjects.

Methods
In this double-blind study, subjects were randomized 3:1 to receive IV BCV or placebo in sequential single ascending dose cohorts (Table 1). Plasma PK samples were collected over 7 days and assayed by HPLC-MS. Plasma BCV PK parameters were determined by non-compartmental analysis and dose proportionality was assessed. Safety assessments were collected over 14 days.

Results
Forty healthy male subjects (18–46 years, 83% White) were enrolled and completed the study. Plasma BCV Cmax and AUC∞ increased in proportion to dose (Table 1). AEs and alanine aminotransferase (ALT) elevations were dose- and infusion duration-related (Table 1). GI AEs were mild. All AEs and ALT elevations were transient and no serious AEs occurred.

Conclusion
Single doses of BCV 10–50 mg administered as a 2h IV infusion were well tolerated and not associated with significant clinical or laboratory abnormalities. BCV IV 10 mg and BCV IV 50 mg achieved geometric mean plasma BCV AUC∞ similar to and 4.5-fold, respectively, values achieved with BCV oral 100 mg tablets (Cmax = 251 ng/mL and AUC∞ = 1394 ng hours/mL). These data support evaluation of repeat dose administration in healthy subjects and virally-infected patients.

Disclosures
M. B. Wire, Chimerix: Employee and Shareholder, Salary. M. Morrison, Chimerix: Employee and Shareholder, Salary.M. Anderson, Chimerix: Employee and Shareholder, Salary. T. Arumugham, Chimerix: Employee and Shareholder, Salary. J. Dunn, Chimerix: Employee and Shareholder, Salary. O. Naderer, Chimerix: Employee and Shareholder, Salary.
Human Coronavirus Circulation in the USA, 2014‒2017
Authors: Biggs Holly M , Killerby Marie E , Haynes Amber K , Dahl Rebecca M , Gerber Susan I , Watson John T 
Published: October 2017

Abstract

Background
Human coronaviruses (HCoV) OC43, 229E, NL63 and HKU1 commonly cause upper respiratory tract infections, but can also cause severe lower respiratory tract disease. Increased use of diagnostic assays for respiratory viruses has facilitated detection and, since 2014, voluntary reporting of HCoV to the National Respiratory and Enteric Virus Surveillance System (NREVSS).

Methods
We reviewed weekly aggregate test results for HCoV OC43, 229E, NL63 and HKU1 voluntarily reported to NREVSS by U.S. hospital and clinical laboratories from July 1, 2014‒April 30, 2017. Laboratories reporting any HCoV result using PCR were included, and the weekly percentage of positive HCoV tests by type was calculated. For a subset of HCoV detections reported to NREVSS via the Public Health laboratory Interoperability Project (PHLIP), which collects individual-level demographic data, we described age distribution and sex. Age distribution by HCoV type was compared using the Kruskal–Wallis test.

Results
154 laboratories, across all 9 U.S. census divisions, reported 834,742 tests for HCoV; 18,514 (2.2%) were positive for HCoV-OC43, 8,363 (1.0%) for HCoV-NL63, 6,828 (0.8%) for HCoV-229E, and 5,170 (0.6%) for HCoV-HKU1. The percentage of tests positive for HCoV generally peaked between December and March (Figure 1). HCoV-OC43 showed distinct annual peaks with variation in magnitude by year. HCoV-HKU1 and NL63 had similar patterns, each with notable peaks during winter 2016 compared with 2015 or 2017. HCoV-229E showed a discernable peak in 2017 compared with the previous 2 years. Of 20,533 individuals with HCoV test results reported via PHLIP, 1,589 (7.7%) tested positive for any HCoV; 50% of HCoV-positive individuals were male, and the median age was 22 (range 0–96) years. Age distribution differed between HCoV types (P &lt; 0.01, Figure 2).

Conclusion
Over approximately 3 seasons, peak positivity for HCoV occurred during winter months, and annual differences in circulation by HCoV type were observed. Continued testing and surveillance for HCoV will allow for further characterization of circulation trends over time and by geographic region, and improved understanding of the contribution of HCoV to the winter respiratory virus season.

Disclosures
All authors: No reported disclosures.
Evaluation of Serum TNF-alpha, IL-6, IL-10, and IFN-gamma Levels in Patients with Crimean–Congo Hemorrhagic Fever
Authors: Hülya Yilmaz , Yilmaz Gürdal , Kostakoglu Ugur , Arslan Mustafa , Karahan Süleyman Caner , Koksal Iftihar 
Published: October 2017

Abstract

Background
Crimean–Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. Cytokines plays an important role in the pathogenesis of viral, bacterial, and immunologic diseases. This study aimed to investigate the role of TNF-alpha, IL-6, IL-10, and IFN-gamma levels in the severity of infection and clinical outcome of patients with CCHF.

Methods
Patients with confirmed CCHF were divided into two groups (severe cases: Patients who exhibited hemorrhage during their hospital stay, and mild/moderate cases: Patients who displayed no hemorrhage during their hospital stay). Demographic characteristics, laboratory tests on admission of all patients with CCHF were investigated, and serum TNF-alpha, IL-6, IL-10, and IFN-gamma levels were measured.

Results
A total of 154 patients with confirmed CCHF were investigated. Forty-six (29.9%) of these patients were in the severe group. In patients with severe CCHF, significantly higher serum levels of TNF-alpha (68.2 ± 23.5; P = 0.008) and IL-6 (73.1 ± 41.6; P = 0.003) were detected, compared with cytokine levels in patients who mild/moderate CCHF (Table 1). No differences in serum IL-10 and IFN-gamma levels between patients who severe CCHF and those who mild/moderate CCHF were detected (P &gt; 0.05).

Conclusion
Cytokines, chemokines, and other inflammatory mediators function in a manner, acting on many different cell types to regulate the host’s immune response. When cytokines present in high concentrations, they might toxic or even lethal effects. In accordance with this view, we have detected increased serum TNF-alpha, IL-6 levels in the patients with severe CCHF.

Disclosures
All authors: No reported disclosures.
Frequency of Epstein–Barr Virus Genotypes in Pakistani Trangender SexWorkers
Authors: Salahud Din Sadia 
Published: October 2017

Abstract

Background
Transgender community large association with sex work has put them at a greater risk of contracting sexually transmitted infections (STIs).The aim of this study was to investigate the prevalence of Epstein–Barr Virus (EBV) genotypes in transgender sex workers (TSWs) of twin-cities of Pakistan. The high prevalence of EBV-2 genotype in sex workers has been previously reported. EBV genotypes were investigated in transgender sex workers to find out EBV-2 occurrence in Pakistani population.

Methods
A total of 86 transgender (Hijras) sex workers were randomly included in this study. Demographics, including age, the number of sex partners, sexual habits, and awareness about protective methods were obtained. Blood was collected from all subjects and The presence of Human Immunodeficiency Virus, Hepatitis B and C virus were determined by antibody strip testing. EBV detection and genotyping were performed by extracting genomic DNA from all whole blood samples. Β-globin and EBNA-1 were amplified to assess the quality and presence of EBV DNA. Analysis of EBNA-2 genotyping was done by nested PCR.

Results
HIV was the most prevalent infection in 40 transgender sex workers (46.51%) followed by HCV in 15 (17.44%). Among HIV-seropositive TSW’s, EBV genotype determination was only achievable in 60% of cases, where 62.5% were EBV-1, 29.16% of EBV-2 and co-infection was found in 8% samples. Among HIV-negative individuals, 78% were EBV-1, whereas EBV-2 genotype and co-infections were absent. All non-typable samples were amplifiable for the EBNA-1 gene in both populations, confirming EBV genome in the samples.

Conclusion
EBV-1 was the most common genotype of EBV in HIV seropositive and seronegative TSW’s but the high occurrence of EBV-2 and co-infection of both types was observed only in HIV seropositive individuals. This is the first report of frequency of EBV infections in the HIV-positive transgender community of Pakistan.

Disclosures
All authors: No reported disclosures.
Estimated Hospitalization Rates for Seasonal Influenza in Adults and Children in Middle Tennessee using a Capture-Recapture Method
Authors: Ivey Kelsey S , Zhu Yuwei , Halasa Natasha B , Schaffner William , Campbell Angela P , Garg Shikha , Ferdinands Jill M , Talbot H Keipp 
Published: October 2017

Abstract

Background
Ongoing surveillance of influenza activity is important to monitor variation in disease severity and vaccine effectiveness, but surveillance systems have limitations. The capture-recapture method aims to more comprehensively estimate disease burden by combining data from independent studies.

Methods
Residents of 8 counties in Middle TN hospitalized with influenza during the 2015-16 influenza A(H1N1pdm09)-predominant season were identified using data from 3 independent CDC-sponsored programs. The Influenza Hospitalization Surveillance Network/Emerging Infections Program (FluSurv-Net/EIP) identifies adult and pediatric cases based on a positive clinician-ordered influenza test. The U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the New Vaccine Surveillance Network (NVSN) enroll adults (3 hospitals) and children (1 hospital), respectively, with respiratory symptoms with/without fever, and obtain nasal/throat swabs to identify cases of influenza; 2015–2016 was a pilot year for HAIVEN. Using the numbers of matched and unmatched cases detected by two studies, a capture-recapture analysis estimated the total number (N) of influenza-related hospitalizations in the population (Table 1). Due to small sample size, the Chapman equation was used, where N = ((a + b + 1)(a + c + 1)/(a + 1)) – 1. The capture–recapture estimates were adjusted for the hospitals’ market share for acute respiratory illness in middle TN residents (69.2% for children and 23.9% for adults) based on hospital discharge data.

Results
Capture-recapture analyses based on unadjusted crude data are shown in Figure 1A and 1B. Age-specific rates of hospitalization were then calculated (Figure 1C).

Conclusion
Using a capture–recapture method, we estimated influenza hospitalization rates of 0.87 (95% CI 0.06–1.68) and 0.80 (95% CI 0.62–0.98) per 1,000 persons among children and adults, respectively.

Disclosures
N. B. Halasa, sanofi pasteur: Research Contractor, Research support. Astra Zeneca: Research Contractor, Grant recipient. W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. H. K. Talbot, Gilead: Investigator, Research support. MedImmune: Investigator, Research support. sanofi pasteur: Investigator, Research support. VaxInnate: Scientific Advisor, Consulting fee. Sequirus: Scientific Advisor, Consulting fee.
Clinical Characteristics of Parainfluenza Virus Infection among Healthy Subjects with Influenza-like Illness
Authors: Fairchok Mary , Chen Wei-Ju , Mor Deepika , Schofield Christina , Arnold John , Danaher Patrick , Deiss Robert , Lalani Tahaniyat , Rajnik Michael , Malone Leslie , Grigorenko Elena , Stalons Donald , Burgess Timothy , Millar Eugene , Coles Christian 
Published: October 2017

Abstract

Background
Parainfluenza virus (PIV) is a chief cause of croup. Less is known about the role of PIV in causing influenza-like illness (ILI) among healthy adults and children. We evaluated clinical characteristics of PIV compared with influenza (flu) infection in healthy subjects diagnosed with ILI.

Methods
The Acute Respiratory Infection Consortium (ARIC) conducted an observational, longitudinal study of ILI at five US military treatment facilities from 2009 to 2016. Participants were otherwise healthy military members, retirees, and their dependents. Symptom data were captured prospectively on days 0, 3, and 7 by interview and patient diary. Nasopharyngeal specimens were collected for etiologic determination by multiplex assay (Diatherix Laboratories, LLC.) Severity scores were calculated for upper respiratory, lower respiratory, GI, composite and systemic symptoms

Results
PIV did not account for a large proportion of ILI in our population with 43/961(4.7%) PIV+ vs. 153/961(15.9%) that were flu+. Age &lt; 5 years was associated with increased detection of PIV (10% in &lt;5 years vs. 3.2% in 5–65 years, P &lt; 0.01). Additionally, on multivariable analysis, the presence of a child aged &lt;5 years in the household was associated with an increased risk of PIV detection (OR = 2.58; 95% CI:1.39, 4.80). Sex, geographic location, year of detection, race/ethnicity, smoking status and obesity were all unrelated to PIV detection. Codetections occurred in 8/43 (18.6%) subjects, but codetected viruses did not show any specific pattern, with 5 different viruses found. When comparing demographic characteristics of ILI caused by flu vs. PIV, the only difference was that flu+ subjects were more often ≥5 years (P &lt; 0.01). Comparing symptom profile and severity of adults with PIV + ILI vs. flu+, we found no differences in the presence or severity of 20 symptoms, nor in severity scores for each of the 5 categories. Rates of hospitalization, antibiotic use, or duration of illness were also indistinguishable.

Conclusion
This is one of a few studies to detail the clinical characteristics of PIV presenting as ILI in healthy subjects. PIV is more often detected in young children with ILI. Although PIV was detected 25% as often as flu, it had an indistinguishable clinical course from influenza associated ILI in adults.

Disclosures
L. Malone, diatherix: Employee, Salary. E. Grigorenko, Diatherix Laboratories: Employee, Salary. D. Stalons, Diatherix Laboratories: Employee, Salary.
Clinical and Economic Burden of Respiratory Viral Infections in Hematopoietic Stem Cell Transplant Recipients: The MD Anderson Experience
Authors: Ghantoji Shashank S , Karanth Siddharth , El Haddad Lynn , Park Anne , Lairson David , Chemaly Roy F 
Published: October 2017

Abstract

Background
Respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus (Flu) are common respiratory viral infections (RVIs) implicated in hematopoietic stem cell transplant (HSCT) recipients. Despite their possible association with high rates of pneumonia and mortality, their clinical and economic burden has not been well studied.

Methods
HSCT recipients with documented RVI who were treated at our institution between September 2012 and October 2015 were included in the study. We used Vizient (formerly University Health Consortium) clinical database to collect and compare total costs, including length of stay, ICU admission rates, intravenous immunoglobulin use, steroid use, and mortality rates among RVIs in HSCT recipients. Encounter-specific demographics, risk factors, underlying cancer, and outcomes were also collected. Multiple linear regression analyses were applied to identify predictors of higher total cost associated with RVI in HSCT recipients at MD Anderson.

Results
Average total cost per encounter was $49,371 for RSV, $29,679 for PIV, and $15,077 for Flu. A total of 1,636 hospitalization days (d) were attributed to these RVIs with an average of 7 d per RSV, 8 d per PIV, and 5 d for Flu infection. The average ICU admission rate was 12% for RSV, 9% for PIV, and 4% for Flu. Around 11% of total RVI encounters had active graft-vs.-host disease at the time of their RVI. Out of the patients with upper respiratory infection, 20% RSV, 44% PIV, and 21% Flu progressed to pneumonia during the 28 d of the study period. Of the 246 total RVI encounters, overall all-cause mortality rate was 6% (RSV: 8% [8/98], PIV: 1% [1/70] and Flu: 8% [6/78]). Length of stay, ICU admission, and receiving intravenous immunoglobulin were strong predictors of higher cost for all RVIs.

Conclusion
This study underscores the significant impact of RVIs in terms of economic and clinical burden in HSCT recipients. Major differences in total costs per encounter across the three RVIs were observed. This cost and clinical data may be helpful for future cost effectiveness studies in this population.

Disclosures
All authors: No reported disclosures.
Vaccinating High-Risk Pediatric Patients and Their Families in the Hospital Setting: Give It a Shot!
Authors: Barros Rebecca , Gornick Wendi , Tran M Tuan , Huff Beth , Singh Jasjit 
Published: October 2017

Abstract

Background
Hospitalization and hospital-based clinics confer an opportunity to target high-risk patients and their families who would benefit from vaccination.

Methods
CHOC Children’s Hospital is a tertiary-care hospital in Southern California with 11,995 admissions in 2016, including 1,580 hematology/oncology (HO) admissions. We examined the trend in influenza vaccine administration in hospitalized and HO patients over the last decade. We assessed the trend in Tdap and influenza vaccine administration among parents of hospitalized children. We correlated those trends with disease outbreaks in the community and educational and programmatic efforts at our institution.

Results
After educational efforts, the influenza vaccination rate in 2017 compared with 2006 increased 13-fold in hospitalized patients and increased 9-fold among hospitalized HO patients. During the H1N1 pandemic in 2009, influenza vaccination rates increased 470% from the year prior (Figure 1). The number of influenza vaccines administered in the clinic to HO patients was 494 and 408 in 2015–2016 and 2016–2017, respectively. Following program initiation, the number of Tdap vaccines administered to parents during their child’s hospitalization increased from 57 doses in 2013 to 118 doses in 2016. The trend in vaccination roughly followed pertussis outbreak cases (Figure 2). The number of influenza vaccines administered to parents of HO patients during their child’s clinic visit increased from 44 doses given in 2015–2016 to 306 doses given in 2016–2017 (Figure 3). At our institution, among staff we achieved a 98% vaccination rate for Tdap and influenza in 2017. There were no serious adverse events reported after patient, parent or staff vaccination during this time period.

Conclusion
Missed opportunities for vaccination of high-risk children include hospitalization and specialty clinic visits. Creating a culture of vaccination and public perception of vaccine importance during outbreaks can increase the influenza vaccination rate among high-risk, hospitalized and HO patients. Programs targeting families of high-risk patients are an opportunity to cocoon a vulnerable population. Vaccination of hospitalized children, their parents and staff is safe in these settings.

Disclosures
All authors: No reported disclosures.
Indications for Antibiotic Orders: How Accurate Are They?
Authors: Heil Emily , Pineles Lisa , Morgan Daniel , Harris Anthony D , Thom Kerri 
Published: October 2017

Abstract

Background
Documentation of antibiotic indications at the time of ordering can provide helpful information for antimicrobial stewardship programs to track antibiotic utilization patterns and improve antibiotic prescribing. Yet accuracy of indications is not fully understood; antibiotics are often ordered empirically without a clear-cut indication, and orders are not often updated once a diagnosis has been made, or the first listed option may be chosen for convenience. As hospitals are implementing antibiotic indications at the time of order entry to meet stewardship standards, our study sought to assess the accuracy of indications in an antibiotic order compared with true indication for the drug.

Methods
Indications for antibiotics, selected from a standardized list, are a required field in the computerized order entry system at our institution. Study investigators, including at least one infectious diseases attending, performed an in-depth post-hoc review to assess antibiotic indication and appropriateness. The frequency that the true antibiotic indication, as assessed by study investigators, matched with the indication in the antibiotic order was analyzed.

Results
Of 396 antibiotic orders reviewed by the study team, 100 had discordant indications between what was written in the order and the investigator-assessed indication (25.3%). The highest rates of discordance were seen with GU-UTI (11/18 incorrect, 61.1%) followed by bacteremia/sepsis (44 of the 116 incorrect, 37.9%). For GU-UTI, the most common investigator assessed true indications were pulmonary including CAP, HAP and empyema. For bacteremia/sepsis, the discordance was often due to a more specific diagnosis or source being identified.

Conclusion
Discordant indications between what was entered at the time of initial order compared with an investigator assessed indication occurred frequently. This finding is of concern as evaluations of antibiotic appropriateness, utilization and benchmarking by the antimicrobial stewardship team rely on the accuracy of indications in the system. Entering a revised indication during an antibiotic time out could improve the accuracy of antibiotic indications and antimicrobial stewardship data.

Disclosures
All authors: No reported disclosures.
Population-Level Hepatitis C Testing Using A Personal Electronic Health Portal System Significantly Improves Screening Rates in Baby Boomers
Authors: Hojat Leila , Kaelber David , Avery Ann 
Published: October 2017

Abstract

Background
Hepatitis C virus (HCV) infection is a major public health burden. The USPSTF and CDC have both released guidelines which recommend screening the baby boomer population (individuals born between 1945 and 1965) given the overrepresentation of HCV infection in this cohort. However, screening rates remain low despite prior attempts at improvement.

Objective
To improve HCV testing rate in the birth cohort in compliance with national guidelines without increasing primary care provider workload or alert fatigue.

Methods
We developed a population health initiative that employed EHR-based tools involving direct patient messaging and bulk lab test ordering via a personal electronic health portal system. This was completed independent of a face-to-face interaction between the patient and provider.

Results
We collected data on 1,024 patients total (514 in the intervention group and 510 in the control group) over a 12-week period. We found a statistically significant higher test completion rate within the intervention group vs. the control group after this initiative was launched: 33.7% in the intervention group (173/514) vs. 19.0% in the control group (97/510) (p-value &lt;0.0002, OR 2.16, 95% CI 1.62–2.88). Bulk lab ordering appeared to have a large impact while bulk messaging appeared to have a less significant role.

Conclusion
To our knowledge, this is the first EHR-based population health initiative to involve obtaining blood work without a direct face-to-face encounter between the provider and patient. This methodology has a broad range of applications including any recommended screening or disease-specific testing, and it will be essential for health systems to adopt similar protocols as we progress toward a pay-for-performance reimbursement model.

Disclosures
All authors: No reported disclosures.