bluuebunny/crossref_metadata_2025_split huggingface dataset:
2439. The role of positive externalities in economic evaluations of new antibiotics: modeling the impact of reduced transmission in healthcare facilities
Authors: Nelson Richard , Samore Matthew H , Jernigan John A , Slayton Rachel , Toth Damon 
Published: October 2019

Abstract

Background
Positive externalities - beneficial spillover effects enjoyed by individuals who are not the primary consumers of a good - are rarely considered in cost-effectiveness analyses (CEAs) of antimicrobial drugs that could reduce person-to-person transmission of the target pathogen. We developed a compartmental model to simulate the effect of 2 hypothetical antibiotics targeting carbapenem-resistant Enterobacteriaceae (CRE) among hospital inpatients: one that treats bloodstream infections (BSIs) and one that decolonizes carriers. We assessed the contribution of positive externalities to the results of CEAs of these 2 antibiotics in the model.

Methods
Our model tracked patients according to CRE carriage, clinical infection, and detection status. Rates of CRE acquisition depended on transmissibility of carriers in different states and were calibrated to data from long-term acute care hospitals. For the BSI treatment scenario we assumed the new drug would decrease the death rate and transmissibility of patients after CRE BSI onset. For the decolonization scenario we assumed the new drug would increase clearance of CRE carriage after clinical detection. For each scenario, we quantified the drug’s effect on the number of BSIs and deaths among patients receiving the drug (direct effect) and among all patients (total effect, i.e., direct plus indirect effect) compared with usual care. For the CEAs, the effectiveness outcome was life-years (LYs) gained and we assumed the new drug cost of $4,000 per dose and cost of a CRE BSI of $24,788.

Results
For both the BSI treatment and decolonization scenarios, the total effect of introducing the new drug was greater than the direct effect alone, indicating the existence of positive externalities. Relative to usual care, the new drug led to a decrease in incremental cost and an increase in incremental effectiveness (see Figures 1 and 2).

Conclusion
The inclusion of positive externalities in CEAs can have important effects on whether these new antibiotics are deemed cost-effective, due to their potential for interrupting chains of transmission. In our model, the inclusion of these effects reduced the incremental cost and increased the incremental effectiveness of these antibiotics.

Disclosures
All authors: No reported disclosures.
2442. Detection of Prosthetic Hip and Knee Joint Infections Using Administrative Databases – A Validation Study
Authors: Kandel Christopher , Jenkinson Richard , Davey Roderick , Widdifield Jessica , Hansen Bettina , Muller Matthew P , Daneman Nick , McGeer Allison 
Published: October 2019

Abstract

Background
Forming large cohorts to study prosthetic joint infections (PJIs) is a challenge without an existing surgical registry, as is the case in Canada. Administrative databases are an option, yet PJI diagnostic codes are insensitive. There is a need to improve the detection of PJIs from within administrative databases.

Methods
Individuals who had a primary arthroplasty at four hospitals in Toronto, Canada from 2010 to 2016 were identified using Canadian Classification of Health Intervention codes (based on the International Classification of Disease, Tenth Revision). Each re-admission to the same hospital until December 31, 2016 was reviewed for the presence of a PJI. The performance characteristics (sensitivity, specificity, positive and negative predictive values) of combinations of diagnostic and procedure codes when compared with the gold standard of chart review were calculated. The primary outcome was the algorithm that maximized sensitivity and positive predictive value.

Results
27,843 primary arthroplasties were performed with 8595 readmissions, of which 572 involved a PJI. Median follow-up was 1258 days (interquartile range (IQR) 614–1891 days), with median time to first re-admission of 352 days (IQR range 166–725 days). PJI codes exhibited a sensitivity of 0.86 (95% confidence interval (95% CI) 0.83–0.89) and positive predictive value (PPV) of 0.89 (95% CI 0.86–0.92). The best performing algorithm is a combination of a PJI code or joint spacer insertion procedure code or insertion of a peripherally inserted central catheter along with an arthroplasty code (sensitivity 0.90, 95% CI 0.88–0.93 and PPV 0.89, 95% CI 0.86–0.91). Using timing from primary arthroplasty, spacer insertion codes and presence of a subsequent arthroplasty procedure code identified 68% (71/105) of first stage and 74% (108/146) of debridement with joint retention procedures during the first re-admission for a PJI.

Conclusion
Combinations of diagnosis and procedure codes can reliably identify PJIs from administrative databases. Individual orthopaedic procedure codes and timing from primary arthroplasty can inform the surgical procedure performed. This PJI detection algorithm could be used for PJI surveillance and research.

Disclosures
All authors: No reported disclosures.
2447. Impact of Agency-Level Policies and Priorities upon Infection Prevention and Control in the Home Environment: Perspectives of Home Health Staff
Authors: Chastain Ashley , Pogorzelska-Maziarz Monika , Stone Patricia , Shang Jingjing 
Published: October 2019

Abstract

Background
Infection prevention and control (IPC) is becoming a national priority in home healthcare (HHC) industry. However, little is known about the impact of agency-level policies and priorities upon IPC practices in the home environment. This qualitative study aimed to explore: 1) how home health agencies (HHA) are implementing IPC policies, and 2) perspectives of HHC staff on agency-level IPC policies and priorities and how they impact patient care.

Methods
From March to November 2018, we recruited staff from HHAs across the United States to participate in in-depth, telephone interviews. HHAs were purposively sampled based on high or low Quality of Patient Care star rating and other agency characteristics from 2016 Provider of Services and Home Health Compare data. Interviews were conducted with 41 staff from 13 HHAs, including administrators, IPC and quality improvement personnel, registered nurses and home health aides. Interview guides were tailored toward the role of the interviewee. Interview transcripts were coded and themes were identified using content analysis.

Results
Themes included: 1) “Handwashing is our priority”; 2) Innovative approaches to care coordination and IPC; (3) Monitoring staff compliance; and, (4) Opportunities for improvement. Almost all HHC staff described that handwashing was a primary focus of IPC policies and staff education at their agencies. Some staff depicted creative ways that their agency was coordinating patient care among staff who were not always in the office, and also unique approaches to educating staff about IPC policies and practices. Administrators and managers explained the ways that they monitored staff compliance around IPC policies, while nurses and aides described how the monitoring reminded them about proper procedures. Finally, HHC staff mentioned various ways in which care coordination, staff education and compliance could be improved at their agencies; for example, more frequent supervisory visits were perceived as a way to improve compliance with agency policies and practices.

Conclusion
This study increases our understanding of the impact that agency-level IPC policies and practices have upon HHC staff and patient care, in addition to specific approaches to care coordination, staff education and compliance monitoring.

Disclosures
All authors: No reported disclosures.
2488. Virologic Failure in ART Naïve Patients Initiating on a Dolutegravir or Elvitegravir-Based Regimen
Authors: Wohlfeiler Michael , Schulman Kathy , Fusco Jennifer S , Punekar Yogesh , Mills Anthony , Priest Julie , Oglesby Alan , Fusco Gregory 
Published: October 2019

Abstract

Background
Robust pharmacoeconomic modeling is dependent on high quality inputs, preferably from randomized clinical trials (RCT), but not all needed head to head comparisons occur in RCTs. We compared virologic outcomes in an antiretroviral (ART) naïve population initiating a dolutegravir (DTG) or elvitegravir (EVG)-based regimen using clinical trial-like criteria.

Methods
ART-naïve adults, initiating a DTG- or EVG-based regimen and meeting all study eligibility criteria (Figure 1) were identified in the OPERA® Observational Database, a collaboration of HIV caregivers following 100,000+ people living with HIV (PLWH) through electronic medical records. PLWH were followed from the date of first prescription until DTG- or EVG discontinuation, death, or study end (July 31, 2018). The primary outcome was verified (2 consecutive viral load (VL) ≥200 copies/mL or 1 VL ≥200 copies + discontinuation) virologic failure (VF), defined as either failure to achieve suppression (<50 copies/mL) prior to 36 weeks or failure to maintain suppression once achieved. Survival analyses were conducted with Kaplan–Meier methods and multivariate Cox Proportional Hazards modeling.

Results
A total of 1,688 (DTG) and 2,537 (EVG) met all eligibility criteria. Median (IQR) length of follow-up in the DTG users was 21 months (14–30), in the EVG users was 20 (14–32) months. Figure 2 characterizes baseline demographic/clinical characteristics. Figures 3 and 4 depict Kaplan–Meier curves and Cox model results, respectively. VF was experienced by 8.2% DTG and 10.9% EVG initiators at a rate (95% CI) per 1,000 person-years of 40.2 (33.8, 47.8) and 51.3 (45.3, 58.1), respectively. Younger age (18–25), being African American, having a baseline CD4 count ≤ 200, or having a government-based payer (ADAP, Ryan White, Medicaid, or Medicare) at baseline were associated with a significant (P < 0.05), increased hazard of VF. Initiating on DTG or initiating therapy with a lower baseline VL was associated with a significant, reduced hazard of VF. Compared with DTG, the adjusted hazard ratio for VF was 1.29 (95% CI: 1.02, 1.63) for EVG.

Conclusion
Among ART-naïve patients, DTG users were significantly less likely to experience virologic failure than EVG users after adjustment for important baseline covariates.

Disclosures
All authors: No reported disclosures.
2493. Real-World Utilization of Ibalizumab (IBA) Without an Optimized Background Regimen (OBT)
Authors: Bouchard Jeannette , Derrick Caroline , Horvath Joseph 
Published: October 2019

Abstract

Background
It is difficult to treat multidrug-resistant (MDR) human immunodeficiency virus (HIV). Trogarzo® (ibalizumab) a novel monoclonal antibody was approved in 2018 for heavily treatment-experienced HIV patients. Data support IBA use with at least one fully active agent, an OBR. Real-world IBA data are lacking. We report a successful case of reaching and maintaining suppression with IBA in a patient without an OBR.

Methods
Mutations were reviewed for the patient, Table 1, and evaluated for treatment. The patient is a 52- year old male, diagnosed in 1994, with MDR HIV secondary to non-adherence. Upon re-presenting to care, the patient was non-compliant with ART. Genotypic interpretation via the Stanford/ANRS algorithm was performed and interpreted, resulting in the addition of IBA intravenous administration every other week. IBA was obtained through patient assistance and costs were covered by the institution for infusion.

Results
Evaluation of the resistance profile indicated varying resistance to all available ART. More specifically, high-level resistance to all FDA-approved INSTIs, PIs, and low to high-level resistance to all NNRTIs and NRTIs. Table 2 outlines the ART history and viral load (VL) trends. The patient was initiated on daruanvir/ritonavir twice daily, etravirine twice daily, emtricitabine/tenofovir alafenamide and did not reach suppression. IBA was added off-label to a failing regimen. The patient reached VS (VL < 200 copies/mL) at Week 4 and has had an undetectable VL for 8 weeks. Notably his CD4 count has risen to 46, first detectable number since re-presenting to care.

Conclusion
We describe a heavily treatment experienced patient with an MDR HIV virus who achieved an undetectable VL without an OBT and the addition of intravenous IBA. Fostemsavir, was utilized in IBA’s phase III trial for similar patients, however, it is not currently FDA-approved nor available. Further data are needed to ensure continued susceptibility to IBA without an OBT. This patient required high-level coordination to reach each visit and receive this therapy alongside his oral agents. We conclude, IBA has allowed this patient to reach and maintain VS.

Disclosures
All authors: No reported disclosures.
2502. Impact of Pharmacist-Led Antiretroviral Therapy Simplification Initiative in Heavily Treatment-Experienced Patients on Virologic Control
Authors: Jimenez Humberto R , Natali Kayla M , Suh Jin S 
Published: October 2019

Abstract

Background
It is well established that antiretroviral therapy (ART) with a lower pill burden are associated with better virologic suppression. However, many HIV providers are cautious when considering ART changes in heavily treatment-experienced patients for a variety of reasons: accumulation of complex resistance patterns, intolerance concerns with new agents, drug-interaction concerns, and a paucity of data on ART simplification in this population. The objective of our study was to evaluate the impact of pharmacist-led initiative to simplify ART among heavily treatment-experienced patients with high pill burdens on virologic control.

Methods
This was a prospective, observational cohort at a clinic in Paterson, NJ, USA. Patients were eligible if: heavily treatment experienced (≥10 years on ART with history of failure or resistance), ART with ≥ 4 pills daily, ≥ 48 weeks of data, and at clinic from September 2016 to present. The primary endpoint was to measure the effect of ART simplification (decrease of ≥ 2 pills daily) on virologic response (HIV RNA < 200 copies/mL) compared with continuation of regimens with a high pill burden. Secondary endpoints included difference in antiretroviral pill burden and monthly cost, based on average wholesale price (AWP).

Results
There were 94 patients eligible for the analysis. Most patients were male (65%), and either Black (53%) or Latinx (35%). The simplification and continuation groups had similar baseline characteristics: mean age (50 vs. 50 years old), daily pill burden (4.77 vs. 4.95), virologic response (82% vs. 87%), CD4 count (459 ± 265 vs. 528 ± 273), monthly ART cost ($4,585 vs. $4,159). M184V (50.0%) and K103N (23.4%) were the most commonly documented mutations. Thymidine-analog, atazanavir-associated, and darunavir-associated mutations were documented in 28.7%, 24.5%, and 11.7% of patients, respectively. Patients with ART simplification were more likely to have virologic response than patients continued on the baseline regimen (97% vs. 76%, P = 0.0126), and had a significantly lower daily pill burden (2.05 vs. 4.95, P = 0.001).

Conclusion
Pharmacist-led ART simplification in heavily treatment experienced patients can dramatically reduce pill burden while achieving better virologic success.

Disclosures
All authors: No reported disclosures.
2506. Trends of Transmitted Resistance Mutations to Four Drug Classes, HIV-Subtypes And Herpesviruses Replication Among Subjects Recently Diagnosed as HIV Infected Over 2004–2019
Authors: Basso Monica , Parisatto Beatrice , Stagni Camilla , Zago Daniela , Pozzetto Irene , Scaggiante Renzo , Cruciani Mario , Ferretto Roberto , Manfrin Vinicio , Francavilla Ermenegildo , Panese Sandro , Sarmati Loredana , Dal Bello Federico , Andreoni Massimo , Palù Giorgio , Parisi Saverio G 
Published: October 2019

Abstract

Background
to evaluate circulation of drug resistance mutations (DRMs), sub-types (ST) and Herpesviruses replication among subjects recently diagnosed as HIV infected (pts) in Veneto (Italy), over 16 years, comparing previously reported trends with the most recent one, updated to 2019.

Methods
on plasma from 2919 patients diagnosed from July 2004 to April 2019, protease (PR), reverse transcriptase (RT) and recently Integrase (In) were analyzed for DRMs, susceptibility profile (Stanford db) and ST. Potential low-level resistances were excluded. CMV-DNA and EBV-DNA were evaluated by in-house Real-Time-PCR in PBMCs.

Results
in 5 periods (2004/06, 07/09, 10/12, 13/16, 17–19) 334, 796, 752, 750 and 287 patients were recruited; non-B-ST were 21.9, 29.3, 33, 32.7 and 48.1% (33.5% Italians in 17–19), respectively. A significant increase of non-B-ST (P < 0.0001 for trend) and of the percentage of Italians with non-B-strains (P = 0.029) were observed. Resistance to PR or to multiple classes declined but not to non-nucleoside RT inhibitors (NNRTI) (Fig 1). E138A alone, not included in the previous evaluations, increased from 2.3 to 1.8, to 3.2, to 3.6, to 4.7% in 2017-19. No primary TDRM to In-Inhibitors (InIn) were found in 469 B-ST-Pts enrolled in 2014–19; 16% had major TDRM for RT/PI. Among 231 non-B patients, 12,5% with other TDRMs, only a 143C and a 66I were found. Accessory InIn-TDRMs were detected (Figures 2 and 3). Nevertheless, from 2009 to 2019 in Veneto 114 InIn-failed and potentially transmitters patients with In-DRMs were found. In 2017–19 17,3% of patients had CMV-DNA in PBMCs, with a median CD4 of 55 (8%), HIV-RNA 247251 cps/mL and EBV-DNA of 811 cps/106 PBMCs (3% were neg); Patients CMV-DNA-negative (82,7%) had median CD4 of 334 (18,9%), HIV-RNA 47770 cps/mL and a significantly lower EBV-DNA of 194 cps/106 PBMCs (15% were neg): differences between immuvirological variables were significant.

Conclusion
An increase of non-B strains and a slight increase of TDRMs among B-ST were observed. The persistent circulation of NNRTI-DRMs, the shortage of major In-TDRMs but a circulation of many In-polymorphisms have implications on the screening at baseline and on the selection of the first-line HAART. Many patients with lower CD4 and higher HIV replication has an incomplete control of co-infecting herpesviruses, which contribute to immunoactivation.

Disclosures
All authors: No reported disclosures.
2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
Authors: Theresa Dungca Nina , Schwem Brian , Arevalo Geraldine , Francisco Christian , Penalosa-Ramos Christine , Ching Patrick , Leyritana Katerina , Destura Raul , Lim Jodor , Tactacan-Abrenica Rosario , Telan Elizabeth , Solante Rontgene , Samonte Genesis , Trinidad Lyka , Mendoza Kevin , Alejandria Marissa M , Salvana Edsel Maurice T 
Published: October 2019

Abstract

Background
Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents.

Methods
We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database.

Results
ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs.

Conclusion
ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable.

Disclosures
All authors: No reported disclosures.
2527. Improving Care for Adolescents Living with HIV: Evaluating the Impact of Case-Based Education
Authors: Hurst Simi Thomas , Blatherwick Don 
Published: October 2019

Abstract

Background
The CDC estimates that 26% of the approximately 50,000 people newly diagnosed with HIV in 2010 were youth 13 to 24 years of age. Older children and adolescents now comprise the largest population cared for at pediatric HIV clinics.

Methods
To improve HIV/ID specialists’ ability to develop a comprehensive care strategy for adolescents living with HIV, a CME/ABIM MOC/CE certified, case-based, educational program was developed. A series of multiple-choice questions evaluated the application of evidence-based recommendations. A “test then teach” approach elicited cognitive dissonance, with evidence-based feedback provided following each learner response. Educational effectiveness was assessed with a repeated-pairs pre-/post-assessment study design; each individual served as his/her own control. A chi-square test assessed changes pre- to post-assessment. P values < 0.05 are statistically significant. Effect sizes were evaluated using Cramer’s V (< 0.05 modest; 0.06–0.15 noticeable effect; 0.16–0.26 considerable effect; > 0.26 extensive effect). The activity launched on a website dedicated to continuous professional development on November 27, 2018. Data for this initial analysis were collected through February 27, 2019.

Results
To date, 6,755 HCPs (1,714 physicians; 2,795 nurses; 1,076 pharmacists) have participated in the activity. Data from the subset of HIV/ID specialists (n = 87) who answered all pre-/post-assessment questions during the initial study period were analyzed. Following activity participation, significant improvements were observed in the proportion of HIV/ID specialists who answered all assessment questions correctly (5% pre vs. 68% post; P < 0.0001; V = 0.397). Improvements were also observed in several specific areas of assessment (table). Additionally, 43% of HIV/ID specialists indicated they planned to modify their treatment approach among adolescents as a result of participating in the education.

Conclusion
Participation in this online, interactive, case-based, educational intervention significantly improved HIV/ID specialists’ ability to develop individualized strategies for adolescents living with HIV. These findings highlight the positive impact of well-designed online education.

Disclosures
All authors: No reported disclosures.