bluuebunny/crossref_metadata_2025_split huggingface dataset:
2093. Utilizing Implementation Science to Identify Barriers and Facilitators to Implementing Harm Reduction Services in the Veterans Health Administration (VHA)
Authors: Harvey Leah , Sliwinski Samantha K , Flike Kimberlee , Boudreau Jacqueline , Gifford Allen L , Branch-Elliman Westyn , Hyde Justeen 
Published: December 2022

Abstract

Background
Rising rates of substance use, particularly synthetic opioids, have led to increases in fatal overdoses and injection-associated infections. Harm reduction, including infection prevention via provision of supplies and education, is an approach to minimize risk of severe outcomes. Although harm reduction services (HRS) are highly evidence-based, implementation in most healthcare settings is limited. The aim of this study was to identify facilitators and barriers to the implementation of HRS to inform strategies for increasing access and adoption of a comprehensive bundle of harm reduction resources within the VHA.

Methods
Qualitative interviews were conducted using a semi-structured interview guide and explored how harm reduction is currently understood and implemented by VHA providers and was designed to identify perceived gaps and barriers. Data were analyzed using a directed content analysis. After barriers and facilitators were identified, they were mapped to relevant implementation strategies using the Consolidated Framework for Implementation Research - Expert Recommendations for Implementing Change (CFIR – ERIC) tool.

Results
15 interviews with VHA providers (physicians, social workers, pharmacists, and directors of addiction and mental health services) were conducted across 5 sites. Multiple barriers and few facilitators to the provision of HRS were identified (Table 1). Currently, HRS were thought to be fragmented and dependent on the knowledge, time, and comfort level of individual providers. Participants also highlighted stigma around substance use, limited support, and burdensome regulatory requirements. Existing infrastructure, social programming, and local champions were highlighted as facilitators. Given these factors, implementation strategies that may be bundled to promote adoption of HRS include engagement of champions, communications and educational strategies, existing policies, and creation of dashboards and tracking and feedback systems (Table 1).

Conclusion
HRS are effective, evidence-based, and patient-centered tools. Mapping of barriers to evidence-based implementation strategies may help improve integration of HRS into VHA healthcare, however, challenges addressing stigma remain a substantial barrier.

Disclosures
Westyn Branch-Elliman, MD, MMSc, DLA Piper,LLC/Medtronic: Advisor/Consultant|Gilead Pharmaceuticals: Grant/Research Support.
2197. Genomic Surveillance for Human Adenovirus Infections among Department of Defense Beneficiaries in the 2018-2019 Season
Authors: Pollio Adam , Fries Anthony C , Yang Yu , Hughes Jerry , Fung Christian , Conte Matthew , Collins Natalie , Macias Elizabeth A , Hang Jun 
Published: December 2022

Abstract

Background
Human adenoviruses (family Adenoviridae, genus Mastadenovirus) (HAdV) species B, C and E cause acute respiratory illnesses (ARI). In particular, respiratory HAdV types 3, 4, 7, 11, 14, 21 and 55 were associated with ARI outbreaks in the US and in other countries. The risk of outbreaks can be effectively controlled by implementation of the live HAdV types 4 and 7 vaccines or mitigated by screening and preventive measures.

Methods
During the influenza season 2018 – 2019, the DoD Global Respiratory Pathogen Surveillance Program (DoDGRS) received 24,300 specimens from its surveillance network. In total, 322 (1.3%) respiratory specimens were positive for HAdV in molecular assays. HAdV samples that produced positive cytopathic effects (CPE) in subsequent viral cultivation were subjected to next-gen sequencing (NGS) for genome sequence assembly, HAdV genome typing, whole genome phylogeny, and sequence comparative analyses to identify sequence insertions, deletions and amino acid mutations.

Results
Out of 166 viral culture samples available for NGS, whole genome sequences were obtained for 161 isolates. A variety types of HAdV were identified, including HAdV-1 (N = 15), HAdV-2 (N = 26), HAdV-3 (N = 60), HAdV-4 (N = 13), HAdV-5 (N = 6), HAdV-6 (N = 3), HAdV-7 (N = 12), HAdV-14 (N = 10), HAdV-55 (N = 1), and HAdV-56 (N = 1). HAdV types 4, 7 and 14, which were reported causing ARI outbreaks in the US military and other congregate settings, were found in clustered cases in several US states. Comparative sequence analyses of these isolates revealed the emergence of novel genetic mutations despite the stability of adenovirus genomes.

Conclusion
Routine clinical respiratory pathogen diagnostics or molecular surveillance of respiratory diseases detect adenovirus without determination of HAdV type. Human adenoviruses are genetically diverse and can infect a number of tissues with severities varied from mild to fatal. Enhanced genomic surveillance of HAdV in the US and worldwide will shed light on prevalence, genetic divergence, and viral evolution of human adenoviruses and inform timely risk assessment and countermeasures.

Disclosures
All Authors: No reported disclosures.
2207. Rates of Lower Respiratory Tract Infections Among US Adults Aged ≥18 Years With and Without Chronic Medical Conditions
Authors: Weycker Derek , Averin Ahuva , Houde Linnea , Ottino Kevin , Shea Kimberly M , Gessner Bradford D , Yacisin Kari , Curcio Daniel , Begier Elizabeth , Rozenbaum Mark 
Published: December 2022

Abstract

Background
While it is widely recognized that older adults and adults with chronic medical conditions are at increased risk of lower respiratory tract infections (LRTI), available evidence on the magnitude of increased risk is limited.

Methods
A retrospective observational cohort study using IBM MarketScan Commercial/Medicare Databases (2016–2019) was conducted. The study population included all adults (age ≥ 18 years) and was stratified by age and comorbidity profile (with vs. without high-risk conditions, based on recommendations for influenza vaccination in the United States). LRTI was ascertained on an overall basis as well as by causative pathogen (e.g., respiratory syncytial virus [RSV]) based on corresponding diagnosis codes, and was classified based on care setting (hospital, emergency department [ED], physician office/hospital outpatient [PO/HO]). Incidence rates (and relative rates [RRs]) were generated by age, and within each age group, by comorbidity profile.

Results
Using adults aged 18-34 years as the reference, RR of LRTI generally increased with older age across care settings, with the most marked increase for hospitalizations: for hospitalized-LRTI, RRs ranged from 1.7 for 35-49 years to 78.9 for ≥ 85 years; for ED-LRTI and PO/HO-LRTI, RRs ranged from 1.0 to 3.4 and from 1.4 to 2.1, respectively (Table). Within age groups, LRTI rates were also consistently higher among adults with versus without high-risk conditions: for hospitalized-LRTI, RRs ranged from 9.9 to 21.1; for ED-LRTI, from 2.3 to 3.2; and for PO/HO-LRTI, from 1.6 to 2.5. Age-specific RRs of hospitalized-LRTI due to RSV were largely comparable to overall LRTI results; age-specific RRs for other care settings, and RRs for adults with versus without high-risk conditions across care settings, were generally higher for LRTI due to RSV.

Conclusion
LRTI incidence, especially for events requiring acute inpatient care, is markedly higher among older adults and adults of all ages with chronic medical conditions. Effective vaccines against respiratory pathogens could help reduce this elevated risk of LRTI.

Disclosures
Derek Weycker, Ph.D., Pfizer Inc.: Grant/Research Support Ahuva Averin, M.P.P., Pfizer Inc.: Grant/Research Support Linnea Houde, M.S., Pfizer Inc.: Grant/Research Support Kevin Ottino, M.H.S., Pfizer Inc.: Grant/Research Support Kimberly M. Shea, Ph.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Kari Yacisin, M.D., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Daniel Curcio, M.Sc., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds Mark Rozenbaum, Ph.D., M.B.A., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds.
LB1528A. Fluvoxamine for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial
Authors: McCarthy Matthew W 
Published: December 2022

Abstract

Background
The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild-to-moderate coronavirus 2019 (COVID-19) is unclear. Tolerability has also been identified as a potential limiting factor for 100 mg twice daily of fluvoxamine. We evaluated the efficacy of low-dose fluvoxamine 50 mg twice daily for 10 days compared with placebo for the treatment of early mild-to-moderate COVID-19.

Methods
ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged ≥ 30 years, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to fluvoxamine 50 mg twice daily for 10 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28.

Results
Of those eligible for the fluvoxamine arm, 675 were randomized to and received fluvoxamine; 619 received concurrent placebo. Sixty-six percent of the study population reported at least 2 doses of a COVID-19 vaccine. There was no evidence of improvement in time to recovery with fluvoxamine compared with placebo (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86–1.06; posterior probability for benefit [HR &gt; 1]=0.2). Sixteen participants (2.4%) in the fluvoxamine arm had urgent care or emergency department visits or were hospitalized compared with 11 (1.8%) in the pooled, concurrent placebo arm (HR 1.5, 95% CrI 0.5–3.0; posterior probability for benefit [HR &lt; 1]=0.1725). No participant in either arm was hospitalized, and no deaths occurred. Adverse events were uncommon in both arms.

Conclusion
Treatment with low-dose fluvoxamine 50 mg dosed twice daily for 10 days did not result in improved time to recovery among outpatients with COVID-19 in the United States during the delta and omicron variant surges.

Disclosures
All Authors: No reported disclosures.
146. Heteroresistance to cefiderocol among Pseudomonas aeruginosa clinical isolates harboring changes in TonB-dependent receptor pathways and AmpC
Authors: Egge Stephanie L , Rizvi Samie A , Simar Shelby R , Dinh An , Hanson Blake M , Arias Cesar A , Cecilia Tran Truc , Miller William R 
Published: December 2022

Abstract

Background
Cefiderocol (FDC) is an iron siderophore cephalosporin with activity against multi-drug resistant (MDR) Gram-negative bacteria. Despite high rates of in vitro susceptibility, treatment failure with the emergence of resistance is still a concern. Heteroresistance, or the presence of a resistant sub-population in a strain that tests susceptible by standard methods, has been suggested as a potential mechanism for this observation. Previously, we showed that MDR Pseudomonas aeruginosa (PA) with changes in the iron siderophore transporters (TBDR) responsible for FDC uptake had decreased zone diameters on Kirby-Bauer (KB) testing as compared to MDR-PA with wild-type TBDRs. Here, we investigated the prevalence of heteroresistance (HR) among TBDR mutants using population analysis profile-area under the curve assay (PAP). Table 1.Pseudomonas aeruginosa strain characteristicsFigure 1.PAP-AUC results of Pseudomonas aeruginosa TBDR mutants v. non-mutant controls

Methods
Previously sequenced MDR-PA isolates were selected for the presence of mutations in TBDR genes within the primary FDC import pathways (pirA, pirRS, piuA, piuD). Isolates harboring pre-existing TBDR mutations (n=12) were compared with wild-type P. aeruginosa strain PA01 and 5 MDR-clinical isolates harboring wild-type TBDRs. FDC MICs were performed by broth microdilution (BMD) in iron depleted media (IDM). For PAP, isolates were grown overnight in IDM before serial dilution and plating on agar with increasing concentrations of FDC. Agreement between BMD, KB, and PAP-AUC HR detection was assessed.

Results
On BMD, 10 of 12 TBDR isolates tested susceptible to FDC (MIC range ≤0.5-2 µg/mL), and all control isolates had an MIC ≤0.5 µg/mL (Table 1). None of the control strains were HR per PAP (Fig 1). However, in the TBDR group, 50% of isolates showed either a resistant (n=2) or HR (n=4) phenotype. Resistance occurred in the setting of both TBDR mutations and either an exogenous β-lactamase (OXA-15 variant) or AmpC variant (PDC-205). Of the HR isolates, one had a change in AmpC Ω-loop (E221K), while the other three had only the PirR frameshift mutation. BMD was not able to identify any of the HR isolates.

Conclusion
A greater number of MDR-PA with TBDR mutations showed resistance or HR to FDC than MDR-PA controls with wild-type TBDRs. Mutations in TBDRs could be a marker for FDC non-susceptibility and potential therapeutic failure.

Disclosures
Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support William R. Miller, MD, Entasis Therapeutics: Grant/Research Support|UpToDate: Royalties - Topic Contributor.
251. Clinical Features and Outcomes of Pneumothorax and Pneumomediastinum in COVID-19
Authors: Adusumilli Sangeeta , Bhargava Ashish , Franco Rene 
Published: December 2022

Abstract

Background
Pneumothorax (PTX) and pneumomediastinum (PM) have been reported among hospitalized patients with COVID-19. It can occur among patients breathing spontaneously or as a result of barotrauma from invasive positive-pressure ventilation or from medical procedures. We aim to study the clinical features and outcomes of pneumothorax and pneumomediastinum within 48 hours of hospitalization among COVID-19 patients.

Methods
We conducted a multicenter retrospective study among the hospitalized adults with COVID-19 who had pneumothorax and pneumomediastinum within 48 hrs. of admission between November 2020 and December 2021. Cases were identified using ICD 10 codes. Electronic medical records were reviewed after Institutional Board approval.

Results
We identified a total of 21 patients, 12 (57%) only had PTX, 6 (28%) only had PM, and 3(14%) had both. Mean age for the cohort was 57 yrs, 13 (62%) were females, and 14 (67%) were whites. Chronic lung and end-stage renal diseases were noted among 9 (43%) patients followed by obesity in 9 (43%) and diabetes in 4 (19%). A total of 12 (57%) patients have smoked tobacco. At the time of hospitalization, 12 (57%) patients had oxygen saturation ≤94% and 9 (43%) had ≤90%. PTX and PM on admission chest x-ray were noted in 12(57%) and 4 (19%) respectively. 3 (14%) developed them after intubating and/ or after BiPAP. Patients were treated with steroids (90%), remdesivir (62%), interleukin-6 inhibitors (24%), and convalescent plasma (9%). Chest tube was placed in 7 (33%) patients and thoravent in 1 (5%) patient. Complications were septic shock (14%) and deep venous thrombosis (10%). There were 4(19%) deaths.

Conclusion
Spontaneous PTX can be a presenting sign for COVID-19. We noted higher complications and mortality among the COVID-19 patients with PTX and PM than reported in literature. Clinicians should be aware of this potential occurrence, requiring close monitoring and aggressive management. Larger studies can further validate the findings of our study.

Disclosures
All Authors: No reported disclosures.
345. Performance Evaluation of the LifeScale AST Rapid Automated Antimicrobial Susceptibility System
Authors: Snyder James W , Chaudry Nadia , Hoffman Wesley 
Published: December 2022

Abstract

Background
Reducing the time for antimicrobial susceptibility test (AST) results directly from positive blood cultures is essential for managing patients with suspected sepsis/bacteremia caused by the most predominate Gram-negative bacteria. The aim of this study was to evaluate the LifeScale AST system using a custom LifeScale 96-well broth microdilution panel. The system employs a microfluidic sensor that detects and measures the mass of individual organisms at high throughput with MIC results available within 4-6 hours.

Methods
Fresh blood cultures detected as positive by a continuous monitoring blood culture system and confirmed by Gram stain for Gram-negative rods were enrolled in the study. If a mixed Gram stain was observed, the sample was ineligible for the study. Testing was performed within 12 hours of the blood culture being flagged as positive. LifeScale performance was evaluated by comparing MICs and interpretive results to the MicroScan Walkaway 96. The following metrics were assessed: Essential Agreement (EA), Category Agreement (CA), Very Major Discrepancy (VM), Major Discrepancy (M), and Minor Discrepancy (Min).

Results
A total of 65 samples were tested that met criteria for LifeScale (intended) claimed species: E. coli (N = 45), Klebsiella pneumoniae (N = 9), Pseudomonas aeruginosa (N = 8), Klebsiella aerogenes (N = 2), and one isolate each of Acinetobacter lwoffi, Acinetobacter species, and Klebsiella oxytoca. Three organisms, 2 E. coli, one P. aeruginosa, were excluded due to insufficient growth or amplitude error. The average time to results was 4.31 hours. Following resolution of discrepant AST results, there was 97.92% final agreement between LifeScale and MicroScan Walkaway 96, 36% categorical agreement, no very major discrepancies, and 0.16% major discrepancies.

Conclusion
The LifeScale system provided reliable AST results for Gram-negative organisms directly from positive blood cultures with minimal hands-on time (approximately less than 8 minutes), allowing for more rapid antimicrobial management compared to standard methods. This is the first AST system that detects and measures the mass of each organism compared to traditional growth-based AST methods. Results for additional organisms will be provided once development is complete.

Disclosures
All Authors: No reported disclosures.
357. Risk Factors and Antifungal Susceptibility Pattern of Candida parapsilosis Candidemia: A Single centre Observation study from Central India.
Authors: Garg Rahul , Wankhade Archana B , Das Padma 
Published: December 2022

Abstract

Background
Candida parapsilosis infection has recently emerged as an important antifungal-resistant nosocomial pathogen having the unique ability to grow on inanimate objects and surfaces. The aim of this study was to analyze the predisposing conditions, outcome, and antifungal susceptibility pattern of candidemia due to C. parapsilsosis complex.

Methods
A single-center retrospective observational study from January 2019 to December 2021 of all cases of candidemia was carried out at an 890-bedded University Hospital in central India. Data regarding demographic characteristics and clinical risk factors were collected from the patient’s medical records. Antifungal susceptibility testing was performed; MIC results were interpreted according to CLSI breakpoints (M27-A3). Risk factors and outcome association at the species level were analyzed by using Fisher’s exact test.

Results
Of 211 patients diagnosed with Candidemia during the study period, 53 (25.1%) were infected with C. parapsilosis which represented the second most frequently isolated yeast after C. albicans (n=98; 46.4%). A total of 26 (49%) C. parapsilosis isolates were non-susceptible to fluconazole (NSF), which included resistant (n = 20) and susceptible dose-dependent (n = 06) isolates. The median patient age was 63 years.15.3% were neonates. The majority of patients (90%) suffered from multiple comorbidities, diabetes mellitus (43%) being the commonest. A total of 55 % of patients underwent surgical intervention within 30 days from the onset of candidemia. Univariate logistic regression revealed that ICU admission (odds ratio [OR] 2.45), central venous catheter use (OR 2.46), renal impairment (OR 1.687) were more common among FNS isolates than fluconazole-susceptible (FS) isolates (all P &lt; 0.05). The overall crude mortality at 30 days was 36%; higher in patients infected with FNS isolates than FS isolates.

Conclusion
There is an increase in the absolute number of invasive infections by C. parapsilosis observed over the past 2 years. At this moment, the percentage of fluconazole non-susceptible C. parapsilosis is very high and poses a threat to infected patients and has a clinical impact in our hospital. Being able to identify and treat infections caused by this pathogen is important to prevent clinical outbreaks.

Disclosures
All Authors: No reported disclosures.
434. Healthcare Personnel Interactive Pathogen Exposure Response System
Authors: Smith Lauren , Fallon Susan , Virk Zunaira , Salinas Alejandra B , Curless Melanie , Cosgrove Sara E , Maragakis Lisa , Rock Clare , Klein Eili ,   CDC prevention epicenter program
Published: December 2022

Abstract

Background
Infectious disease exposure investigations in the hospital are labor-intensive for the infection prevention and control (IPC) team and vulnerable to healthcare personnel (HCP) recall bias. We developed an electronic health record (EHR) algorithm to identify and rank patient-HCP interactions based on the likelihood and intensity of exposure.

Methods
We compared conventional and EHR-based findings from seven exposure investigations conducted between November 1, 2020 and February 1, 2022 at The Johns Hopkins Hospital (JHH), a 1095 bed academic tertiary center in Baltimore, MD. Conventional exposure investigations were conducted for hospitalized patients who tested positive for SARS-CoV-2 while not in COVID-19 isolation precautions. IPC contacted department managers to identify and report potentially exposed HCPs to occupational health. The EHR-based method identified HCP-patient interactions based on clinical data such as documentation in the flowsheet, medication administration, etc. A score was calculated for each HCP based on the estimated duration and intensity of the contact. Genomic sequencing of available samples was performed to investigate transmission events.

Results
Overall, the EHR-based system identified 75% (59/79) of the HCPs identified by conventional exposure investigations and 100% of those who document in the EHR. In contrast, it was unable to identify any potentially exposed individuals who do not document in the EHR (Table 1). All patient-HCP COVID-19 transmissions identified by conventional investigation and confirmed through genomic sequencing were identified by the EHR-based system, and all had high-intensity scores (i.e., top quartile of the list of exposed individuals). Table 1.Comparison of Conventional and EHR Based COVID-19 Exposure Investigations

Conclusion
We found clinical EHR data was highly sensitive and specific in identifying potentially exposed HCPs compared with conventional exposure investigations. The inability to detect interactions with support staff or others who do not document in the EHR was a limitation and suggests that EHR data can augment but not replace conventional exposure investigations. The system’s speed, ease, and lower resource requirements make it a promising tool to more efficiently complete exposure investigations in healthcare settings.

Disclosures
Sara E. Cosgrove, MD, Basilea: Member of Infection Adjudication Committee.