bluuebunny/crossref_metadata_2025_split huggingface dataset:
882. Systematic Underdosing of Oseltamivir in Hospitalized Patients with Influenza
Authors: Bains Ashveen , O'Hara Margaret , Oppenneer Kevin , DeHart Del J 
Published: December 2022

Abstract

Background
Oseltamivir remains the primary treatment for seasonal influenza syndromes and early administration has been shown to increase the clinical benefit of treatment; we studied current practice and describe patient and system variables influencing dosing decisions.

Methods
We reviewed oseltamivir dosing in 135 adult patients in our community hospital admitted with acute influenza over two northern Hemisphere influenza seasons (2016-2017 and 2017-2018) and for whom pharmacy dosing protocols were invoked. We reviewed admitting symptoms for factors suggesting possible dehydration, the timing of treatment in relation to testing for influenza, the estimated creatinine clearance at the time of dose determination for oseltamivir, the initial dose of drug, and dose-adjustment over time.

Results
Patients ranged in age from 27-96 years (mean 74), with 83 males and 52 females among the 135 patients over these two seasons. Testing results were available for 131 patients and 75 (57%) were positive, while 56 (43%) were negative, and therefore treated empirically based on presenting symptoms.
Ninety patients (67%) received an initial dose of 30 mg of oseltamivir, while 45 patients (33%) received an initial dose of 75 mg. Of the 90 patients who were dose-adjusted by the pharmacist to 30 mg for the initial dose, 24 (27%) had a creatinine clearance &gt; 60 mL/min, and it is not clear what factors influenced those decisions. Of the 90 patients with an initial creatinine clearance of &lt; 60 mL/min, 22 (24%) showed a clinically significant improvement to &gt; 60 mL/min within the first 24 hours of hospitalization yet only 8 patients had their dose adjusted. Presenting symptoms did not predict patients who had rapid improvement of creatinine clearance. Of the 45 patients receiving an initial dose of 75 mg of oseltamivir, 19 (42%) had creatinine clearance values of &lt; 60mL/min, and were therefore given a loading dose, followed by dose adjustment.

Conclusion
We found a significant percentage of patients were underdosed initially and dosing was not adjusted for changes in renal function. Reviewing and revising dosing protocols and guidelines may lead to more effective treatment for influenza and may serve as a model for future test-to-treat options for therapies for other acute viral respiratory infections in the future.

Disclosures
All Authors: No reported disclosures.
885. Integrated Blood Culture and Molecular Diagnostic Device Reduces Time-to-Result to a Quarter of Traditional Methods
Authors: Huning Laura , Varma Devika , Jackson Abbey , Bohlen Peter , Ng Rainer , Pamula Vamsee 
Published: December 2022

Abstract

Background
Prolonged antibiotic exposure in infants with negative blood cultures is associated with adverse outcomes, disruption of the developing microbiome, and increased carriage of antibiotic resistance genes. However, early administration of antibiotics significantly reduces risk of infant morbidity and mortality caused by infections, and therefore faster culture-to-identification is highly desirable. We combined blood culture (BC) and PCR-based pathogen identification into a single digital microfluidic (DMF) device to speed up BC results.

Methods
Our DMF BC+PCR device has a custom-built BC bottle incubator, which is connected to a disposable cartridge that performs sample preparation and PCR. Standard BC bottles were inoculated with K. pneumoniae, then incubated in either the DMF BC device or a traditional BC device (BD BACTEC 9050). Samples were drawn from the DMF BC bottle at 3, 4 and 5 hours and loaded in the cartridge for automated sample processing and PCR. Time-to-positivity for the DMF BC+PCR device was determined using cycle threshold and compared with the traditional method, which uses fluorescence from BC bottle followed by PCR on a separate device.

Results
Bacterial presence could be detected as quickly as 3 hours post inoculation (Ct values of 34, 31 and 28 at 3, 4, and 5 hrs) with five replicates of K. pneumoniae samples on the DMF BC+PCR device (growing 10x every hr), compared to &gt; 12 hrs for the traditional method (10.5 hr culture and 2 hr PCR identification). Additionally, for 5 common pathogens that cause neonatal sepsis (K. pneumoniae, E. coli, S. aureus, S. agalactiae, or S. epidermidis), we also demonstrated that the DMF BC bottle incubator and the traditional BC device show similar growth curves using optical methods to determine growth.

Conclusion
The DMF BC system yields bacterial growth rates equivalent to traditional methods, but can drastically reduce time to pathogen identification, from 12 hrs to 3 hrs by leveraging PCR sensitivity to determine growth rather than fluorescence in the BC bottles. To our knowledge, this is the first demonstration of using an integrated microfluidic PCR platform to speed up culture and identification. Further work is ongoing to include antibiotic susceptibility testing and expand the panel of pathogens detected on the same cartridge.

Disclosures
Laura Huning, PhD, Baebies, Inc.: Stocks/Bonds Devika Varma, PhD, Baebies, Inc.: Stocks/Bonds Abbey Jackson, PhD, Baebies, Inc.: Stocks/Bonds Peter Bohlen, n/a, Baebies, Inc.: Stocks/Bonds Rainer Ng, PhD, Baebies, Inc.: Stocks/Bonds Vamsee Pamula, PhD, Baebies, Inc.: Stocks/Bonds.
886. Positive Bacterial Blood Cultures and Time to Positivity in Children: Should Empiric Antibiotics be Reconsidered Sooner?
Authors: Patel Pratik A , Locsin Miguel , Xiang Yijin , Lu Lydia , Fernandez Alfred , Jaggi Preeti 
Published: December 2022

Abstract

Background
Evaluation for bacterial bloodstream infections (BSIs) is often associated with prescribing empiric antibiotics while awaiting blood culture results, typically 48 hours. We examined characteristics associated with positive cultures treated as BSI vs contaminant in children and BSIs associated with prolonged (≥ 24 hours) time-to-positivity (TTP).

Methods
In a retrospective study of children (≤ 21 years) at our pediatric healthcare system, we abstracted demographic, clinical, and blood culture data from the electronic medical record for all initial positive bacterial blood cultures from March 2021 to February 2022. We excluded fungi and cultures collected within 14 days of a previous positive. TTP was calculated from time/date of collection to Gram stain report. Host status was categorized as previously healthy, immunocompromised (IC), and chronic condition/s. A BSI was defined as a positive culture treated for ≥ 3 days. BSI cultures were categorized as Gram-positive definite (GPD) pathogens, other Gram-positive (OGP), Gram-negative (GN), or polymicrobial (PM). Characteristics associated with prolonged TTP for BSIs were identified using mixed-effects logistic regression.

Results
There were 816 positive cultures identified in 697 children, with 582 (71%) treated as BSIs and 536 of those (92%) positive in &lt; 36 hours. Positive cultures drawn with adequate blood volume, in the setting of fever, severe neutropenia, and from IC children were significantly more likely to be treated as BSIs (all p&lt; 0.05, Table 1). The most common BSI was a GN pathogen (34.2%, Figure 1). Characteristics associated with prolonged TTP were absence of fever and cultures drawn peripherally. Early TTP (&lt; 24 hours) was associated with cultures drawn outpatient and growth of high likelihood pathogenic organisms (GPD, GN, PM) compared to OGP (all p&lt; 0.05).
On multivariate analysis, cultures drawn peripherally remained associated with prolonged TTP (p&lt; 0.01), while GPD, GN, and PM cultures remained associated with early TTP (p&lt; 0.01, Table 2).

Conclusion
We found that 92% of clinically significant BSIs in children were identified by 36 hours with BSIs with pathogenic organisms (GPD, GN, PM) associated with TTP &lt; 24 hours. Reassessment of the need for antibiotics after 24–36 hours should be considered.

Disclosures
Pratik A. Patel, MD, Cardinal Health, Inc: Advisor/Consultant.
1542. MR-proADM Biomarker Predicts COVID-19 Clinical Outcomes: a US-based Cohort Study
Authors: Mansour Michael 
Published: December 2022

Abstract

Background
Mid-regional proadrenomedullin (MR-proADM) is a biomarker released following endothelial damage. Our study aimed to investigate baseline MR-proADM as a predictor of a wider range of clinical outcomes of varying severity in patients admitted with COVID-19 from a US-based multicenter trial.
Outcomes Within 28 days Stratified by Binary MR-proADM (Cutoff 0.87 Nmol/L), Number of Events (percentage)
Values expressed as percentages (%) indicate either the proportion of the total population or the respective MR-proADM stratum. Statistical significance between MR-proADM strata was determined by the chi-square test or the Fisher's exact test when applicable. P-Values were not corrected for multiple testing.

Methods
Data from the Boston Area COVID-19 Consortium Bay Tocilizumab Trial (NCT04356937) was used in this study. Patients with biomarker determinations, and not admitted to the intensive care unit (ICU) on admission, were included. MR-proADM cutoff of 0.87 nmol/L was assessed in predicting clinical outcomes.

Results
Out of 182 patients, 11.0% were mechanically ventilated or dead within 28 days. Of patients with MR-proADM &gt;0.87 nmol/L, 21.1% were mechanically ventilated or dead within 28 days, versus 4.5% of those ≤0.87 nmol/L (p&lt; 0.001). The sensitivity, specificity, NPV, and PPV of MR-proADM cut-off of 0.87 nmol/L in predicting mechanical ventilation or death were 75%, 65%, 95%, and 21% respectively, with an AUC of 0.76, outperforming other biomarkers. Specifically, MR-proADM outperformed plasma IL-6 in predicting mechanical ventilation and death.MR-proADM was independently associated with mechanical ventilation or death, ICU admission, prolonged hospitalization beyond day 4, and worsening on the COVID-19 ordinal scale.

Conclusion
MR-proADM functions as a valuable prognostic biomarker in predicting clinical outcomes of patients with COVID-19, outperforming other commonly utilized biomarkers.

Disclosures
Michael Mansour, MD, PhD, ThermoFisher Scientific: Grant/Research Support.
1168. Crimean-Congo Hemorrhagic Fever Virus in Central, Eastern, and South-eastern Asia
Authors: Fereidouni Mohammad , Kuhn Jens H , Apanaskevich Dmitry A , Pecor David , Pshenichnaya Natalia , Keshtkar-Jahromi Maryam 
Published: December 2022

Abstract

Background
Crimean-Congo hemorrhagic fever (CCHF) is endemic in Africa and in areas below the 50th parallel of north (latitude 50°0' N) in Asia and Europe, but the epidemiology of CCHF needs to be better characterized in most regions.

Methods
We comprehensively searched scientific databases for studies on CCHF epidemiology in these regions. We used a One Health approach to describe disease burden through human cases, animal and human serology studies, and Crimean-Congo hemorrhagic fever virus (CCHFV) isolation from ticks. In addition, we leveraged a classification scheme tosort countries into five categories based on the level of evidence and the maturity of their CCHF surveillance systems.

Results
We identified 2,253 CCHF cases that occurred in the region during the period 1944–2021. Central Asian countries reported the majority of cases (1,966). China is the only country in Eastern and South-eastern Asia that reported CCHF cases (287). Six countries (China, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) were assigned to level 1 or level 2, based on the maturity of their surveillance systems. Two countries (Mongolia and Myanmar) were assigned to level 3, due to conclusive evidence of CCHFV circulation in the absence of reported CCHF cases. Subsequently, 13 countries in Eastern and South-eastern Asia were categorized in levels 4 and 5, based on CCHFV vector prevalence.

Conclusion
This paper describes past and present status of the CCHF reporting systems to inform international and local public-health agencies to strengthen or establish CCHF surveillance systems and address shortcomings in the region.

Disclosures
All Authors: No reported disclosures.
1170. Effects of Helminths and Anthelmintic Treatment on Cardiometabolic Diseases and Risk Factors: A Systematic Review
Authors: Pham Khanh , Mertelsmann Anna , Mages Keith C , Kingery Justin , Mazigo Humphrey D , Jaka Hyasinta , Kalokola Fredrick M , Changalucha John , Kapiga Saidi , Peck Robert , Downs Jennifer A 
Published: December 2022

Abstract

Background
Growing evidence suggests a link between helminth infections and cardiometabolic diseases, but their relationships have not been reviewed systematically. Further, the possibility that helminth eradication could increase the risk of cardiometabolic diseases has not been comprehensively investigated.

Methods
We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development or severity of cardiometabolic diseases and risk factors. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and updated on March 1, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently.

Results
Eighty-three studies were included in the final analysis (Figure). Most studies reported on lipids (44), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and cardiomyopathy (4) (Table). Fifteen different helminth infections were represented. Helminth-infected subjects were less frequently reported to have dyslipidemia, metabolic syndrome, diabetes, and atherosclerosis, including coronary artery disease. Only 11 studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment adverse increases in lipids, diabetes or glucose levels, and/or metabolic syndrome. Figure.PRISMA Flow Diagram of Systematic ReviewTable.Trends of Cardiometabolic Diseases and Risk Factors Reported in All Included Studies

Conclusion
Animal and human reports consistently indicate that helminth infection may offer protection against dyslipidemia, metabolic syndrome, diabetes, and cardiovascular disease, and this protection may lessen after anthelmintic treatment. Our findings highlight the need for further cross-disciplinary research, which would have implications for both individual and population health, including mass drug administration, and could point towards ground-breaking new strategies to address the challenges of non-communicable diseases worldwide.

Disclosures
All Authors: No reported disclosures.
1172. Factors Associated With Febrile illnesses in Children in 27 Countries of Sub-Saharan Africa
Authors: Ssentongo Paddy , Chinchilli Vernon M , Shah Khush , Ba Djibril M 
Published: December 2022

Abstract

Background
Evidence on the relative importance of various factors associated with febrile illness in children and their heterogeneity across countries can inform the prevention, identification, and management of communicable diseases in resource-limited countries.
Heatmap of odds ratios.
Country-Specific Odds Ratios for 18 Factors Associated With Febrile illness From Multivariable Adjusted Models.

Methods
This cross-sectional study of 298 327 children aged 0 to 59 months assessed the strengths of associations of 18 factors with childhood fevers, using Demographic and Health Surveys (2010-2018) from 27 sub-Saharan African countries. A total of 7 direct factors (i.e., respiratory illness, diarrhea, breastfeeding initiation; vitamin A supplements; child's age; full vaccination; sex) and 11 indirect factors (household wealth; maternal education; maternal unemployment, water source; indoor pollution, stool disposal; antenatal care; family planning needs; maternal age, rural residence, and maternal marriage status) were assessed. Febrile illness was defined as the presence of fever in 2 weeks preceding the survey.

Results
Among the 298 327 children aged 0 to 59 months included in the analysis, the weighted prevalence of fever was 22.65% (95% CI, 22.31%-22.91%). In the pooled sample, respiratory illness was the strongest factor associated with fever in children (adjusted odds ratio [aOR], 5.46; 95% CI, 5.26-5.67; P &lt; .0001), followed by diarrhea (aOR, 2.96; 95% CI, 2.85-3.08; P &lt; .0001), poorest household wealth (aOR, 1.33; 95% CI,1.23-1.44; P &lt; .0001), lack of maternal education (aOR, 1.25; 95% CI, 1.10-1.41; P &lt; .0001), and delayed breastfeeding (aOR, 1.18; 95% CI, 1.14-1.22; P &lt; .0001. Febrile illnesses were more prevalent in older children &gt;6 months than those 6 months and younger.

Conclusion
In this study, respiratory illness, diarrhea, and socioeconomic conditions were the strongest factors associated with fevers in children of sub-Saharan Africa. Major causes of fevers in sub-Saharan Africa may mostly be attributed to respiratory infections and possibly viral—that may not be treated by antimalarial or antibiotics. Point of care diagnostics are needed to identify the pathogenic causes of respiratory infections to guide the clinical management of fevers in limited-resource countries.

Disclosures
All Authors: No reported disclosures.
1181. Predictive Score for Dengue Infection with Complete Blood Count Parameters, Including the New Monocyte Distribution Width – a Retrospective Single Center Derivation and Validation Study
Authors: Phuttasen Naiyana , Pornprasitsaeng Surapong , Onthong Yupapin , Sinthana Thurdsak , Limvorapitak Wasithep 
Published: December 2022

Abstract

Background
Dengue infection is a differential diagnosis in patients with acute undifferentiated fever. Early detection and management may reduce mortality. Monocyte distribution width (MDW) is a new parameter in complete blood count (CBC). It is recently approved for early detection of sepsis. We have noticed high MDW in Dengue patients. This study aimed to describe MDW changes in Dengue infection and to develop predictive score for early detection of Dengue infected patients.

Methods
We retrospectively retrieved data of adult patients with acute fever who had CBC and Dengue serology (NS1 antigen, IgM and IgG) performed during September 2019 to May 2020 at Thammasat University Hospital. Medical records were reviewed. MDW was compared between groups. Patients were randomly divided into training and validation set. Predictive score was developed from the training set and validated in the validation set with multivariable analysis.

Results
A total of 431 patients, with Dengue infection in 127 patients (29.5%), were included in the analyses. The median (interquartile range) of MDW in Dengue patients were higher than non-Dengue patients [29.7% (26.5 – 34.7) vs. 24.2% (21.1 – 27.8), P &lt; 0.001]. In patients with confirmed Dengue infection, MDW increased with increasing severity (Figure). Training and validation sets included 216 and 215 patients with 64 and 63 Dengue infection, respectively. Independent predictive factors of Dengue infection were white blood cell &lt; 4 x 109 /L (score 1), platelet &lt; 100 x 109 /L (score 1) and MDW &gt; 24% (score 1). No clinical features were independently predictive of Dengue infection. The area under receiver-operating-characteristic curve (95% confidence interval) of the prognostic score in the training and validation set were 0.839 (0.779 – 0.899) and 0.742 (0.674 – 0.811), respectively. With the cut-off score ≥ 1, the sensitivity and specificity of the score were 92.2% and 40.8% in the training set and 88.9% and 44.1% in the validation set.
Monocyte distribution width in Dengue and non-Dengue patients
Box-plot showing monocyte distribution width in patients with Dengue in comparison with non-Dengue (panel A) and compared between each Dengue severity (panel B)

Conclusion
MDW increase in patients with Dengue infection and also increase with Dengue severity. We have developed and internally validated a simple predictive score for Dengue infection based on only results from CBC and MDW. Further large-scale external validation study is required to confirm the utility of our predictive score.

Disclosures
All Authors: No reported disclosures.
1182. Risk factors for colonization with extended-spectrum cephalosporin resistant and carbapenem resistant Enterobacterales among community adults, Bangladesh: An Antibiotic Resistance in Communities and Hospitals (ARCH) study
Authors: Mah-E-Muneer Syeda , Chowdhury Fahmida , Hossain Kamal , Luvsansharav Ulzii-Orshikh , Hassan Md Zakiul , Smith Rachel Mann , Styczynski Ashley R 
Published: December 2022

Abstract

Background
Antimicrobial resistant (AMR) organisms are an increasing global health threat that are spreading within communities. Understanding the risk factors for colonization with AMR organisms is critical for implementing prevention and control strategies, particularly in resource-limited settings such as Bangladesh.

Methods
During 2019, we conducted a population-based observational study in Dhaka (surveillance site of icddr,b). We collected stool samples from randomly selected adults and tested for Enterobacterales with extended-spectrum cephalosporin resistance (ESCrE) and carbapenem resistance (CRE) using selective media followed by VITEK-2 confirmation. Participants completed demographic surveys assessing food consumption, animal contact, sanitation, water sources, and healthcare exposure. We identified factors associated with ESCrE and CRE colonization using bivariable and multivariable logistic regression, adjusting for potential confounders and clustering.

Results
Of 714 enrolled individuals, 557 (78%) were colonized with ESCrE and 66 (9%) with CRE. In bivariable analysis, factors associated with ESCrE colonization included fresh fruit consumption in the past week (OR 1.8, 95% CI 1.2-2.9), public tap as main source of drinking water compared with basic improved source (OR 3.3, 1.0-11.0), and unimproved toilet (pour/flush to open drain, pit latrine without slab) compared with basic improved toilet (OR 11, 2.9-42.0). Only consumption of fresh fruit was significant in the multivariable analysis (aOR 2.0, 1.3-3.2). Factors associated with CRE colonization in bivariable analysis were hospitalization in the last 3 months (OR 3.2, 1.2-8.6), limited sanitation facility (improved toilet shared with other households) (OR 2.0, 1.0-3.8), and limited hygiene (availability of handwashing facility on premises without soap and/or water) (OR 3.3, 1.4-7.7). The only factor that was significant in multivariable analysis was hospitalization in the last 3 months (aOR 3.0, 1.0-8.7).

Conclusion
While ESCrE colonization is common in urban communities, hospitals may be contributing to community spread of CRE. Targeted interventions focused on healthcare facilities may be needed to mitigate the transmission of AMR organisms.

Disclosures
All Authors: No reported disclosures.