bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospitalization and Emergency Room Visits: The Opportunity for Re-Engagement for People Living with HIV/AIDS (PLWHA)
Authors: Almirol Ellen , Schmitt Jessica , Wesley-Madgett Lindsey , Eavou Rebecca , Pitrak David , Ridgway Jessica P 
Published: October 2017

Abstract

Background
Persons living with HIV/AIDS (PLWHA) who are not engaged in HIV medical care are at greater risk for adverse individual health outcomes, as well as potential transmission to others. Thus, detecting and re-engaging PLWHA who are not in care is a public health priority. Unplanned hospitalizations or Emergency Department (ED) visits provide a potential opportunity to re-engage PLWHA who are out of care. Our Data-to-Care (D2C) pilot project was launched in July 2016 to identify PLWHA in the ED and inpatient settings and subsequently, establish re-engagement in HIV care (RIC) among those out of care.

Methods
Our D2C program leverages electronic health records (EHR) as a mechanism to identify PLWHA and support RIC. An Infectious Diseases social worker (SW) generates an EHR-based report daily to identify PLWHA in the hospital in near real-time, then determines whether a patient currently receives HIV care. If not, the SW meets with the patient to determine needs, insurance status, schedules an HIV care appointment, and provides referrals for wraparound services. SW subsequently confirmed attendance at HIV care appointment. RIC was defined as attending an HIV clinical appointment, and X2 analyses were used to compare differences between RIC and not RIC.

Results
Over a 10-month period, we identified 237 PLWHA seen in the ED or hospitalized. The majority of patients were African-American (AA) (92.7%), male (66.1%) and mean age 44.6 ± 14.6 years old. Of the 237 patients identified, 172 (72.6%) confirmed already in care, 7 (3.0%) deceased, and 2 (0.8%) incarcerated. Among patients eligible for RIC, 44 (73.3%) were contacted by staff, 39 (65.0%) were referred to care, and 32 (53.3%) were RIC. Patients not RIC were all AA, 69.2% male, and mean age 38.5 ± 14.2 years old. Patients identified in the inpatient setting were more likely to be RIC vs. those identified in the ED (81.3% vs. 18.8%, P &lt; 0.01). Interestingly, insurance type was not associated with RIC vs. not RIC (P = 0.17).

Conclusion
Our pilot program demonstrates the potential for using the EHR to identify PLWHA who are in need of RIC during unplanned hospitalizations and ED visits. Inpatients were more likely to be RIC than ED patients, likely due to the ability to make in-person contact during hospitalization compared with ED visit by SW staff.

Disclosures
D. Pitrak, Gilead Sciences FOCUS: Grant Investigator, Grant recipient
Healthcare Resource Utilization and Costs Associated with Switching First-line Antiretroviral Therapy among HIV-infected Patients in the United States
Authors: Mao Jianbin , Johnson Micheal , Mcpheeters Jeffrey , Prajapati Girish , Beyer Andrew 
Published: October 2017

Abstract

Background
Initial antiretroviral therapy (ART) is modified for non-virologic failure reasons in many patients, and the healthcare resource utilization (HRU) and costs associated with these switches in the real world is not well understood.

Methods
Administrative claims data from the Optum Research and Impact National Benchmark Databases were utilized. Adult patients (≥18 years) with HIV-1 diagnosis code, and claim for an anchor agent of the protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) class in first-line ART between July 1, 2006 and December 31, 2015 were identified (see Figure 1 for addl. criteria). Patients with a claim for an anchor agent (PI or NNRTI) different from that in first-line ART were defined as switchers, with index date as date of first claim for new anchor agent. Switchers were matched to patients who did not switch (non-switchers) at 1:3 ratio using propensity score matching on patient and first-line ART characteristics. For non-switchers, date following corresponding duration of first-line ART in matched switcher was assigned as index date. Per-patient-per-month (PPPM) all-cause HRU and costs (US$) during switch period (±15 days of index date) were compared descriptively.

Results
11,302 patients met study criteria. After matching, switcher (1,204) and non-switcher (3,612) groups were comparable on mean age (41.9 vs. 41.7 years), percent male (85.8% vs. 82.6%), percent commercial enrollee (96.0% vs. 95.8%), mean Quan-Charlson comorbidity index score (both 0.4), and mean ART pill burden (both 2.2) with standard difference less than absolute value of 10%. During switch period, switchers had higher mean PPPM ambulatory visits (2.30 vs. 1.26), emergency room visits (0.12 vs. 0.06), inpatient stays (0.04 vs. 0.01), and pharmacy fills (4.52 vs. 3.01) than non-switchers (all P &lt; 0.001). Switchers also incurred greater mean PPPM costs during switch than non-switchers, with an additional $2,261/month total cost, and $1,031/month pharmacy cost (Figure 2).

Conclusion
The study gives a more complete view of the burden of switching initial ART with pharmacy costs driving this burden. Assuming some patients will switch regardless of the regimen selected, less expensive initial ART could reduce this burden further.

Disclosures
M. Johnson, Merk & Co: Research Contractor, research funded by Merk; J. Mcpheeters, Merck & Co.: Research Contractor, Sarary from Optum; G. Prajapati, Merck & Co., Inc.: Employee, Salary; A. Beyer, Merck & Co., Inc: Employee and Shareholder, Salary
Management of End Stage Renal Disease in Persons Living with HIV: A Cost-Effectiveness Analysis
Authors: Joe Winston B , Eaton Ellen F 
Published: October 2017

Abstract

Background
HIV+ kidney transplant (KT) for persons living with HIV (PLWH) is both safe and effective, with comparable patient and graft survival rates relative to HIV- KT. The objective of this study was to evaluate the cost-effectiveness of HIV+ KT relative to HIV- KT and dialysis.

Methods
A decision-tree framework was used to assess the cost-effectiveness of the above treatment options for PLWH. Clinical outcomes at 3 years for KT and effectiveness data (expressed in QALYs) were abstracted from previous publications, when available. Costs were assigned from a payer’s perspective using the US Renal Data System and published literature (expressed in 2014 USD). This analysis assumed a three-year time horizon. Sensitivity analyses were explored to understand how changes in 1) acute KT rejection and 2) KT failure impact cost effectiveness. Limitations include small sample size and short follow up time in referenced studies and a lack of health utility data in HIV positive persons with renal failure. We used TreeAge Software (Williamstown, MA).

Results
HIV+ KT was most cost effective ($299,904/QALY) while both HIV- KT ($329,676) and dialysis ($444,645) were dominated, meaning more costly and less effective. Results were sensitive to the higher KT failure (26% vs. 16%) and acute rejection (39% vs. 17%) observed with HIV- KT relative to HIV+ KT. In sensitivity analysis, as HIV+ KT rejection rates approach 20%, HIV- KT becomes a cost-effective option. As HIV+ KT failure rates approach 26%, HIV- KT becomes cost effective.

Conclusion
Despite its limitations, this analysis demonstrates that HIV+ kidney transplantation is a cost-effective alternative for PLWH under certain conditions. As KT outcomes, like graft failure and acute rejection rates, continue to improve, it is likely that both HIV positive and negative KT will be cost-effective alternatives to dialysis.

Disclosures
All authors: No reported disclosures.
HIV Pre-Exposure Prophylaxis (PrEP) Uptake, Initiation, and Persistence in the Detroit Public Health STD Clinic
Authors: Hacker Elizabeth , Cohn Jonathan , Golden Matthew R , Heumann Christine 
Published: October 2017

Abstract

Background
HIV pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool; however, little is known about PrEP uptake, initiation, and persistence among patients prescribed PrEP in STD clinics.

Methods
Between July 2016 and March 2017, STD clinic staff compiled reports detailing the eligibility and initiation of PrEP in the Detroit STD Clinic. Staff called all patients prescribed PrEP to determine whether they had started PrEP, were still on PrEP, and their reasons for never initiating or discontinuing PrEP. We used chi-square tests to evaluate differences in PrEP initiation and discontinuation by age and race, calculated the population’s mean duration on PrEP (persistence), and used proportional hazards regression to assess differences in persistence by age and race.

Results
A total of 161 STD clinic patients were eligible for PrEP, of whom 71 (44%) were prescribed PrEP. Of the 71 patients prescribed PrEP, staff successfully interviewed 45 (63%) a median of 113 days following their receipt of prescription. Thirty-four (76%) interviewed patients had initiated PrEP, of whom 17 (50%) had subsequently discontinued their medication a mean of 92 days (95% confidence interval [CI]: ± 23.8) following receipt of a prescription. Figure 1 illustrates the PrEP care continuum for our clinic. There was no significant difference in PrEP initiation or discontinuation by age or race. There was no significant difference in persistence by race. Ages 18–24 had the shortest mean persistence (62 days, 95% CI: ±37.5), while those ages 35–44 had the longest mean persistence (146 days, 95% CI: ± 47.3) though this was not a significant difference (hazard ratio 0.39, P = 0.28). The most common reason for not initiating or discontinuing PrEP was concern about side effects (29%).

Conclusion
Clinicians in the Detroit STD clinic prescribed PrEP for less than half of PrEP-eligible patients, only 76% of those prescribed PrEP ever filled their first prescription, and the mean duration of use among those who filled a first prescription was under 6 months. Our findings highlight the need for further evaluation of why eligible patients are not prescribed PrEP, intensified support services to encourage PrEP persistence, and improved patient counseling about potential side effects.

Disclosures
All authors: No reported disclosures.
Comfort Discussing HIV Pre-Exposure Prophylaxis with Patients Among Physicians in an Urban Emergency Department
Authors: Tortelli Brett , Char Douglas , Powderly William , Patel Rupa 
Published: October 2017

Abstract

Background
HIV pre-exposure prophylaxis (PrEP) is effective but underutilized in the United States. The emergency department offers an opportunity to access at-risk individuals for PrEP referral. While several studies have described provider awareness and acceptance of PrEP, these studies have focused largely on infectious diseases, HIV, and primary care specialty physicians. Thus, PrEP awareness, knowledge, and concerns among emergency physicians remain unknown. We sought to determine provider comfort in discussing PrEP with patients among emergency physicians in Missouri.

Methods
We conducted an online survey among 88 emergency physicians at Washington University in St. Louis from February 2017 to March 2017 in St. Louis, Missouri. The survey included demographics, comfort discussing PrEP, having ever heard of PrEP (awareness), knowledge of the current CDC prescribing guidelines, concerns with use, and knowing local PrEP referral information. The questions were asked on a Likert scale and dichotomously categorized. We evaluated predictors of physician comfort of discussing PrEP with patients using multiple logistic regression.

Results
Sixty-seven participants completed the survey; 64.1% were faculty. Most (79.1%) were PrEP aware, however, only 23.9% were knowledgeable of current guidelines and 22.7% of referral information. Concerns included lack of efficacy (53.7%), side effects (89.6%), and the selection for HIV resistance (70.1%). Comfort discussing PrEP was 43.3%. When adjusting for the concern of efficacy, having PrEP knowledge (OR: 5.43; CI: 1.19–30.81) and having referral knowledge (OR: 7.82; CI: 1.93–40.98) were significantly associated with comfort in discussing PrEP.

Conclusion
We found moderate PrEP awareness among emergency physicians, but also high levels of discomfort in discussing PrEP with their patients. Future provider training should include addressing misinformation surrounding the concerns with PrEP use and prescribing, reviewing current guidelines, and providing local referral resources for PrEP patient care. Emergency department settings can facilitate PrEP awareness and referral to care among at-risk patients to help reduce national HIV incidence.

Disclosures
All authors: No reported disclosures.
Evaluation of early achievement of an AUC/MIC of &gt;400 for Vancomycin in children with methicillin-resistant Staphylococcus aureus bacteremia
Authors: Murai Takemi , Higuchi Hiroshi , Suwa Junichi , Funakoshi Hanako , Yoneda Ryuu , Ishii Sho , Araki Kotaro , Fukuoka Kahoru , Aizawa Yuta , Horikoshi Yuho 
Published: October 2017

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia causes morbidity and mortality in children. The standard treatment for MRSA bacteremia is vancomycin, which should achieve a 24 hour area under the curve over the minimum inhibitory concentration ratio (AUC/ MIC) of &gt;400. Whether or not attaining AUC/ MIC &gt;400 early in the disease course improves outcomes in children is controversial. The aim of our study was to determine whether early achievement of AUC/ MIC &gt;400 improved outcomes in children with MRSA bacteremia.

Methods
Children whose blood culture grew MRSA between March 2010 and April 2017 at Tokyo Metropolitan Children’s Medical Center were enrolled. The exclusion criteria were no vancomycin administration, use of extracorporeal membrane oxygenation, no data on dosage and vancomycin MIC, and cases of contamination. Susceptibility testing was performed by a microdilution method. The outcomes of patients who achieved an AUC/MIC &gt;400 at the first assessment prior to the Fourth or Fifth vancomycin dose were compared with those of patients who did not. The clinical outcomes were persistent bacteremia on Days 3 and 7, mortality at 30 days, and the recurrence of MRSA bacteremia.

Results
In total 175 MRSA isolates from 50 children were identified. Of these 56 episodes were eligible for enrollment. Forty-one subjects (73.2%) were boys. The median age was 9 months (interquartile range: 1.8–120.5 months). The median initial dose of vancomycin was 40 mg/kg (interquartile range: 30–44.3 mg/kg). Among MRSA isolates, vancomycin MIC of &lt; 0.5 mcg/mL, 1 mcg/mL and 2 mcg/mL were 1 (1.8%), 53 (94.6%) and 2 (3.6%), respectively. Fifteen patients (26.8%) achieved AUC/MIC &gt;400 early. The two groups did not differ significantly in terms of persistent bacteremia on Days 3 (P = 0.96) or 7 (P = 0.82), mortality at 30 days (P = 0.47), or the recurrence of MRSA bacteremia (P = 1.0).

Conclusion
Children with bacteremia who achieved AUC/ MIC&gt;400 early did not differ significantly from children who did not in terms of their clinical outcomes.

Disclosures
All authors: No reported disclosures.
Relationship between Vancomycin Area Under the Concentration-Time Curve (AUC) and Nephrotoxicity in Adults
Authors: Allen David , Townsend Mary , Drew Richard 
Published: October 2017

Abstract

Background
While recent data correlate vancomycin’s ratio of the area under the 24 hour time-concentration curve (AUC0−24h) to the pathogen’s minimal inhibitory concentration (MIC) of &gt; 400 mg*hours/L with a favorable clinical outcome, data are sparse to correlate vancomycin AUC0−24h to nephrotoxicity. Our primary objective was to evaluate the relationship between vancomycin AUC0−24h and nephrotoxicity.

Methods
This single-center, retrospective cohort study was conducted at a large US tertiary-care hospital. Adults hospitalized between 08/01/13 and 08/31/14 with normal baseline renal function receiving intravenous vancomycin ≥ 72 hours were included. Vancomycin AUC0−24h was calculated for each subject utilizing computer-based Bayesian pharmacokinetic methods (BestDose™). Subjects were divided into AUC0−24h of &lt; 700 and &gt; 700 mg*hours/L groups. The primary endpoint of nephrotoxicity (defined as a 50% relative increase or &gt; 0.5 mg/dl absolute increase in SCr over at least 2 consecutive days) was compared between exposure groups. Secondary objectives were to compare the incidence of nephrotoxicity with and without the following risk factors: sepsis, concomitant nephrotoxins, vancomycin troughs &gt; 20 mg/L or doses ≥ 4 g/day, and Charlson Comorbidity Index scores.

Results
Table 1. Multivariate Model of Nephrotoxicity and Clinical Characteristics

Conclusion
A significant increase in nephrotoxicity was observed in patients with a vancomycin AUC0−24h ≥ 700 mg*hours/L. Given that this exposure threshold is within the target for efficacy for organisms with elevated MICs, further studies should be conducted to better delineate the AUC0−24h values associated with nephrotoxicity.

Disclosures
All authors: No reported disclosures.
Clinical Manifestations and Outcome of Fluoroquinolone Associated Acute Interstitial Nephritis
Authors: Farid Saira , AbuSaleh Omar , Mahmood Maryam , Garrigos Zerelda Esquer , Hamadah Abdurrahman , Nasr Samih , Leung Nelson , Sohail M Rizwan 
Published: October 2017

Abstract

Background
Fluoroquinolones (FQ) are among the most commonly prescribed antibiotics. Nephrotoxicity related to FQ use is infrequently reported and the mechanism of renal injury is incompletely elucidated. We describe clinical manifestations and outcome of patients with biopsy proven acute interstitial nephritis (AIN) associated with FQ use at our institution.

Methods
We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic Rochester from 1993 to 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy proven AIN that were attributed to FQ use.

Results
We identified 24 patients with FQ-related biopsy-proven AIN. The most commonly used FQ was ciprofloxacin (71%) with median antibiotic treatment duration of 7 days (Figure 1). The median duration between starting FQ and the diagnosis of AIN was 8.5 (IQR: 17). Common clinical manifestations included fever (50%), flank pain (8%), and skin rash (21%). However, 17% of the patients were asymptomatic at the time of diagnosis (Figure 2). Majority (58%) of the patients recovered following discontinuation of antibiotics and returned to baseline renal function at a median of 20.5 (IQR: 15.5). Six patients required temporary hemodialysis and 9 patients received steroids.

Conclusion
Onset of FQ-related AIN can be delayed and a high index of suspicion is needed by physicians prescribing these agents. Overall outcomes are favorable with recovery to baseline renal function within 3 weeks of discontinuing the offending drug.

Disclosures
All authors: No reported disclosures.
Traditional PK-PD Indices for Efficacy – Can We Do Better?
Authors: Lakota Elizabeth A , Bader Justin C , Bhavnani Sujata M , Andes David R , Ambrose Paul G 
Published: October 2017

Abstract

Background
The relationship between antimicrobial activity and exposure relative to MIC is typically evaluated using one of three PK-PD indices, AUC:MIC ratio, Cmax:MIC ratio, and %T&gt;MIC. However, under certain circumstances, none of these PK-PD indices may be the most optimal. These include when the fitted Hill functions for each of the PK-PD indices do not allow for sufficient discrimination, the variability about the fitted functions is wide, and/or the pattern of dose fractionation data is non-informative. Relationships fit using the traditional PK-PD indices may be suboptimal for drugs which exhibit extreme PK characteristics such as abnormally short or long half-lives. As described herein, we explored the use of a fourth PK-PD index for such instances, AUC/τ:MIC ratio (τ = dosing interval).

Methods
Previously-described ceftolozane dose-fractionation data from a study using a neutropenic murine thigh-infection model were evaluated [AAC 2013; 57(4):1577–82]. In this prior study, mice were infected with E. coli ATCC 25922 (MIC = 0.5 mg/L) or K. pneumoniae ATCC 43816 (MIC = 1.4 mg/L). Ceftolozane doses ranged from 1.56 to 1600 mg/kg/24h given q3h, q6h, q12h, or q24h. Relationships between log10 colony forming units (CFU) at 24 hours and AUC:MIC ratio, Cmax:MIC ratio, %T&gt;MIC, and AUC/τ:MIC ratio were evaluated by pathogen and pooled using Hill-type models and non-linear least squares regression.

Results
For evaluations of data by pathogen, AUC/τ:MIC ratio best described changes in log10 CFU at 24 hours. The coefficients of determination (r2) for these pathogens were improved by 0.20 and 0.11, respectively, relative to the highest r2 achieved using any of the traditional PK-PD indices. Similar results were observed when the data were evaluated using a pooled approach (Figure 1).

Conclusion
AUC/τ:MIC ratio may be useful to evaluate drugs demonstrating the extremes of PK. Accordingly, this PK-PD index best described ceftolozane PK-PD, an agent with a very short murine plasma half-life (&lt;15 minutes). The use of the PK-PD index that allows for the best fit of the data to the Hill function and reduced variability about the fitted function will not only improve the characterization of PK-PD but will also improve the accuracy of future dose selection analyses.

Disclosures
All authors: No reported disclosures.