bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of First-Year Medication Adherence in a National Cohort of Veterans Initiating Pre-Exposure Prophylaxis (PrEP) to Prevent HIV Infection
Authors: Ohl Michael , Richardson Kelly , Beck Brice , Alexander Bruce , Van Epps Puja , Maier Marissa , Lund Brian , Vaughan-Sarrazin Mary 
Published: October 2017

Abstract

Background
Current guidelines for HIV Pre-Exposure Prophylaxis (PrEP) recommend daily use of tenofovir disoproxil fumarate / emtricitabine (TDF/FTC). Little is known about levels and predictors of long-term PrEP medication adherence in routine clinical settings.

Methods
We used a previously-validated algorithm and national Veterans Health Administration (VHA) administrative data to identify a cohort of Veterans initiating PrEP during 2012–2015 (i.e., TDF/FTC use, no other antiretroviral use, and no diagnosis codes for HIV, hepatitis B, or needle-stick injury). We used pharmacy refill data to calculate the proportion of days covered (PDC) by TDF/FTC in the 365 days after initiation, and multivariable logistic regression to identify patient characteristics associated with high adherence (i.e., PDC &gt; 0.80).

Results
Most (96%) of the 706 Veterans initiating PrEP were men, reflecting the overall demographics of patients in VHA. The median age was 38. Reported race in administrative data was 141 (20.0%) black, 485 (68.7%) white, 42 (5.9%) other, and 38 (5.4%) missing. Only 30 PrEP users (4.2%) lived in rural areas. Co-existing diagnoses included substance use disorder in 264 (37.4%), hypertension in 250 (35.4%), and diabetes in 95 (13.5%). The median PDC for TDF/FTC in the first year was 0.78 (IQR 0.41–0.96), and a minority (N = 120, 17%) had only a single TDF/FTC fill. Predictors of high adherence were older age (OR 1.88, 95% CI 1.20–2.84 for age 50–64 compared with age &lt; 35); white compared with black race (OR 1.96, 1.30–2.94), Male sex (OR 4.17, 1.67–12.50), absence of a substance use diagnosis (OR 1.47, 1.05–2.04), and presence of diabetes (OR 1.66, 1.02–2.75).

Conclusion
Adherence to TDF/FTC in the first year of PrEP was overall high. Racial, gender, and substance-use-related differences in PrEP adherence mirrored those previously described for PrEP uptake. Interventions to promote equitable PrEP uptake should include strategies to support adherence.

Disclosures
All authors: No reported disclosures.
Perceptions of HIV Pre-exposure prophylaxis (PrEP) among young pregnant women from KwaZulu-Natal, South Africa
Authors: Guillamet Laia Jimena Vazquez , Moll Anthony P , Kacin Alexa , Madi Jabulile , Ndlovu Ntombi , Shenoi Sheela 
Published: October 2017

Abstract

Background
Pre-exposure prophylaxis (PrEP) is effective for HIV prevention with good adherence. In high HIV prevalence settings, young women ages 18–24 are at high risk of HIV acquisition, particularly during pregnancy and the postpartum period, and would potentially benefit from PrEP. More information is needed to achieve successful implementation of PrEP in this population.

Methods
The study was performed in Tugela Ferry, one of the poorest subdistricts of South Africa. From June-August 2016,the study team interviewed 187 HIV negative pregnant women ages 18–24 anonymously at health care facilities. Interviews collected data on demographics, HIV and PrEP knowledge, HIV risk and readiness for oral PrEP.

Results
Among 187 pregnant women, the mean age was 20.3 years (SD1.97), 179 (95.7%) were unemployed, 93 (49.7%) completed secondary school, and 137 (73.3%) reported one partner in the last month. None reported having ever being paid for sex. While 185 (98%) knew that HIV can be transmitted through sex, only 117 (62.5%) knew that a woman can transmit HIV to her child, and only 95 (51%) knew that HIV can be transmitted through breastmilk. Sixty-eight (36.4%) women believed that a sexual partner had been sexually active with another person in the last month, though 182 (97.3%) had difficulty negotiating condom use with their partner, and only 7 (3.7%) women reported consistent use of condoms. The vast majority (97%) would start PrEP if a doctor recommended it though 100 (53.5%) were concerned about being mistaken for HIV positive.

Conclusion
Pregnant young women in rural South Africa are at risk for HIV acquisition and are interested in PrEP. Knowledge of risks of HIV lags, particularly with regard to mother to child transmission. Young pregnant women are not able to negotiate consistent condom use and need a HIV prevention tool that is within their control. Stigma may be a barrier to effective PrEP use among these women. Further research is needed to guide potential PrEP implementation in pregnant women.

Disclosures
All authors: No reported disclosures.
Microbiology and Clinical Characteristics of Industrial Oil Burns
Authors: Kelly Devin , Rizzo Julie , Yun Heather , Blyth Dana 
Published: October 2017

Abstract

Background
Injured oil workers are exposed to a broad microbiome in hydraulic fracturing fluids (HFF) and oil wells at the time of injury. This includes Pseudomonas, Stenotrophomonas, Acinetobacter, and rare human pathogens which may be harder to culture. This study evaluates oil-related burn (ORB) microbiology.

Methods
Patients admitted to the USAISR burn center enrolled in the Epidemiology of Workplace Burns and Injuries in Texas registry from April 2011 to November 2016 were included as cases and controls. Patients hospitalized ≤2 days were excluded. ORB was defined as exposure to HFF (FORB), or non-HFF (NFORB). Controls were patients admitted with industrial burns (non-ORB). Patient demographics and clinical cultures (days 1–15) were obtained through the registry and electronic medical record.

Results
149 industrial burns were included, of which 35 (23%) were ORB and 114 (77%) were non-ORB. Of the ORB, 11 (31%) were FORB and 24 (69%) were NFORB. ORB had a median age, TBSA, and Baux score of 31, 25, and 58 compared with non-ORB with 36, 4, and 44, respectively (P &lt; 0.01). Twenty-five patients had positive cultures: 12 (48%) non-ORB and 13 (52%) ORB. Sixty Isolates identified from the ORB population included Flavobacterium, Pseudomonas, and Serratia. FORB accounted for three (25%) of the culture positive ORB. S. marcescens was isolated in 1 FORB (33%) compared with 0 NFORB and non-ORB (P &lt; 0.05). Otherwise, there was no statistical difference in isolates. Median time to first positive culture differed among non-ORB (4 days), FORB (13 days), and NFORB (3.5 days, P = 0.03). Forty-six (31%) patients had cultures obtained during admission: three (7%) FORB, 12 (26%) NFORB, and 31 (67%) non-ORB. Of cultured patients, ORB had a median TBSA and Baux score of 44 and 90 compared with non-ORB with 11 and 47, respectively (P &lt; 0.01). Comparing all cultured patients, ORB had more positive, negative, and total cultures compared with non-ORB with 2 vs. 0, 7 vs. 3, and 10 vs. 3, respectively (P &lt; 0.01).

Conclusion
Within this cohort, ORB was associated with more severe injuries compared with non-ORB. They had more positive, negative, and total cultures, and recovery of S. marcescens was associated with FORB. Larger studies with non-culture based technology could help further define the microbiology of this uniquely exposed population.

Disclosures
All authors: No reported disclosures.
Pharmacokinetics of Tedizolid in Adults with Cystic Fibrosis
Authors: Wang Joshua , Park Jenny , Jayne Jordanna , Bensman Timothy , D’Argenio David , Fukushima Lynn , Rao Adupa , Beringer Paul 
Published: October 2017

Abstract

Background
The presence of MRSA in the airways of patients with CF is associated with more rapid lung function decline and a higher mortality. Tedizolid (TDZ) is an oxazolidinone antibiotic with potent activity against MRSA; however, the pharmacokinetics (PK) in CF have not been described. The purpose of this study was to determine the PK of IV/PO tedizolid in plasma in patients being treated for acute pulmonary exacerbations.

Methods
We conducted a prospective, multiple dose, randomized, crossover study. TDZ phosphate was administered as 200 mg IV over 1h or PO once daily x 3 under fed conditions, with a 2-day washout, followed by crossover. Laboratory studies were performed throughout the study as routine clinical care. Blood samples were obtained prior to the Third dose of IV and PO and at 8 additional timepoints over 48 hours. TDZ concentrations in plasma were determined by LC-MS/MS. The maximum concentration (Cmax) and time to maximum (Tmax) were obtained from the measured data. Area-under-the concentration curve (AUC24) was determined using the linear trapezoidal rule. Compartmental PK was performed using ADAPT 5 software. Data are described by mean ± SD.

Results
The patients (4M, 2F) had a mean age of 27 years (22–32), BMI 22.0 ± 4.2 kg/m2, and predicted creatinine clearance of 128 ± 44 mL/minute. There was one report of diarrhea and hoarseness of voice that was unlikely related to the study drug. There were no clinically relevant laboratory changes. The Cmax, Tmax, and AUC24 following IV and PO administration were 2.87 ± 0.64 mg/L / 2.26 ± 0.70 mg/L, 1.32 ± 0.49 hours /2.06 ± 1.29 hours, and 27.1 ± 4.74 mg/L x hours / 25.8 ± 6.03 mg/L x hours respectively. The PK parameters for TDZ were described by a 1-compartment model: Elimination rate constant (Kel) = 0.088 ± 0.014 hour-1, Volume of distribution (V) = 96.4 ± 27.4 L, absorption rate constant (Ka) = 0.869 ± 0.978 hours−1, and bioavailability (F) = 1.00 ± 0.101.

Conclusion
The oral bioavailability of TDZ in patients with CF is complete and the pharmacokinetics are similar to that reported for healthy volunteers indicating no dose adjustments are needed in future studies evaluating the efficacy and safety in patients with CF.

Disclosures
All authors: No reported disclosures.
Therapeutic Drug Monitoring (TDM) of Suspension (SUS), Extended-Release (ER), and Intravenous (IV) Posaconazole (POS) at a Large Transplant Center
Authors: Haidar Ghady , Shields Ryan K , Clancy Cornelius J , Nguyen Minh-Hong 
Published: October 2017

Abstract

Background
Data on ER and IV POS among organ transplant recipients (OTRs) are limited, and the role of TDM is unclear.

Methods
Retrospective study of patients (pt) receiving any formulation of POS who had serum troughs checked. Therapeutic was defined as 3 1 mcg/mL.

Results
We analyzed 88 pt and 340 levels (SUS: 88, ER: 197, IV: 55). Eighty-five pt were OTRs (97%), 73 were lung transplant recipients (LT) (83%), 17 had cystic fibrosis (CF) (19%). POS was used for treatment (70%) (probable aspergillosis (38%), possible aspergillosis (10%), mucormycosis (16%), other mycoses (6%)), prophylaxis (19%), and pre-emptive therapy (14%). POS was given for intolerance of or contraindication to other azoles (47%), salvage therapy (10%), resistance (19%), and failure to achieve therapeutic levels with other azoles (6%). Serum concentration/dose ratios were lower with SUS vs. ER/IV (P &lt; 0.0001) but were similar in ER/IV groups (P = 0.51) (Figure). There was no difference in serum levels between pt receiving ER vs. IV POS at 300 mg once daily (median 1.2 vs. 1.3 mcg/mL, therapeutic 70% vs. 73%, P = 0.57 and &gt;0.99, respectively). 3 pt had levels £ 0.2 mcg/mL on 300 mg ER: 2 had CF and had undergone LT (0.2 and 0 mcg/mL) and 1 had short-gut syndrome (0.1 mcg/mL). Sixty-six percent and 67 % of pt receiving ER or IV POS (300 mg once daily) achieved initial therapeutic levels, respectively; of these, 87% and 83% had median therapeutic follow-up levels, respectively. Serial levels were available for 7 pt whose dose was increased from 300 to 400 mg ER once daily for subtherapeutic levels. 4/7 pt achieved therapeutic levels on 400 vs. 0/7 on 300 mg ER once daily (P = 0.069). Metoclopramide use and CF were associated with subtherapeutic vs. therapeutic levels (25% vs. 4% and 37% vs. 13%, respectively, P = &lt; 0.05). When pt with CF were excluded, neither age nor body mass index were associated with POS levels. CF pt had lower levels than non-CF pt on a dose of 300 mg ER once daily (median 0.8 vs. 1.3 mcg/mL, P = 0.018).

Conclusion
Therapeutic levels are more reliably achieved with ER & IV POS compared with SUS POS. Serial TDM is unnecessary for most, but is recommended for pt with CF or those on metoclopramide. Dose increases may effectively increase levels. Novel dosing strategies are needed for CF.

Disclosures
R. K. Shields, Astellas: Received research funding, Research support. Merck: Received research funding, Research support. C. J. Clancy, Merck: Received research funding, Research support. Astellas: Received research funding, Research support. Cidara: Received research funding, Research support. Astellas: Scientific Advisor, Advisory board. Merck: Scientific Advisor, Advisory board. Cidara: Scientific Advisor, Advisory board. Medicines Company: Scientific Advisor, Advisory board.
Acute Flaccid Myelitis Cases Presenting During a Spike in Respiratory Enterovirus D68 Circulation: Case Series From a Single Pediatric Referral Center.
Authors: Naccache Samia , Bender Jeffery , Desai Jay , Van Tam , Meyers Lindsay , Jones Jay , Mongkolrattanothai Kanokporn , Bard Jennifer Dien 
Published: October 2017

Abstract

Background
In 2014, a global outbreak of Enterovirus D68 (EV-D68) caused severe respiratory disease and was associated with an increase in acute flaccid myelitis (AFM) cases. Despite heightened surveillance, both EV-D68 detection and AFM reporting dropped in 2015. As AFM reporting increased in 2016, we sought to better understand AFM and EV-D68 epidemiology at our institution.

Methods
Chart review of clinical presentation and workup was conducted on patients meeting the case definition for AFM for 2015-16. To determine EV-D68 prevalence at CHLA, samples positive for Rhinovirus/Enterovirus (RV/EV) by FilmArray® Respiratory Panel (FA-RP) in September 2016 were screened for EV-D68 by RT-PCR. Results were compared with a research algorithm developed within the FilmArray®Trend epidemiology software. After establishing accurate EV-D68 prediction, the algorithm was used on historic FA-RP assays to measure EV-D68 prevalence at CHLA in 2015 and 2016.

Results
7 patients with a median age of 3.3 years and no significant past medical history presented with AFM between July 15 - October 15, 2016, while none were identified in 2015. All had acute onset patchy weakness involving mostly the upper limbs and grey matter involvement on MRI. 6/7 reported fever/upper respiratory infection prior to AFM onset. CSF from 7/7 was negative by FilmArray®meningitis/encephalitis Panel and 2/7 were positive for EBV DNA. Further work up on CSF and blood were negative. 4/7 (57.1%) patients were RV/EV positive from respiratory samples and 3 were confirmed as EV-D68 by RT-PCR. IVIG was given in 7/7 cases. Patients were discharged after an average of 8.8 (4.8-13.6) days. The FilmArray Trend monitoring revealed that during the time of AFM presentation in 2016, 226/778 patients tested for respiratory viruses by the FA-RP were positive for RV/EV. Of those, 29.2% (66/226) were positive for EV-D68 compared with 0.02% (2/224) over the same period in 2015.

Conclusion
As shown by CDC surveillance data, we saw a resurgence of AFM cases in 2016 compared with 2015. All 7 patients identified were previously healthy and had persistent weakness at discharge. Cases were accompanied by increases in circulating respiratory EV-D68. Further investigation of the correlation between EV-D68 resurgence and AFM is warranted.

Disclosures
L. Meyers, BioFire Diagnostics: Employee, Salary. J. Jones, Biofire Diagnostics LLC: Employee, Salary. J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium.
Lyme Disease in Hispanics in Long Island, New York: A New Health Disparity in the U.S.
Authors: Khoo Teresa , Spallone Amy , Lier Audun , Abul Yasin , Wellins Anna-Marie , Weinbaum Fredric , Luft Benjamin , Marcos Luis A 
Published: October 2017

Abstract

Background
Lyme disease (LD) is the most commonly reported vector-borne illness in the U.S. A risk factor for acquiring LD is the exposure to outdoors. In Long Island, Hispanics compromise a large share of the outdoor occupational workforce.

Methods
A retrospective chart review was performed in all patients with ICD-9 or ICD-10 diagnostic codes for LD between 2011–2016 in SHH and 2010–2015 in SBUH. Inclusion criteria was defined as a clinical scenario compatible with LD (erythema migrans -EM, arthritis, central nervous system (CNS) involvement, carditis, meningitis) and serological confirmation by western blot according to CDC (SBUH) or Imugen® (SHH) criteria.

Results
Out of 1,026 cases (766 SBUH;260 SHH) that carried a diagnosis of LD, 284 cases (22% Hispanics) met inclusion criteria and were added to final analysis (241 SBUH: 43 SHH). The mean age was 48.8 (SD:17.8) and 48.3 (SD:17.5) years-old in H and NH, respectively (p &gt; 0.05). Most were male (H:62.2%; NH: 54.3%; P = 0.2). In the univariate analysis, headaches were more frequently present in H (42.6%) than in NH (26.6%) (P = 0.015). In the logistic regression analysis, the following symptoms were significantly different between H and NH: headaches (OR 1.17, 96% CI 1.60–6.59, &#x2028;P = 0.001) and peripheral neuropathy (OR 0.38, 95% CI: 0.15-0.96, P = 0.04). Among seasons, H were more frequently diagnosed with Lyme during spring months than NH (H: 26.3% vs. NH: 12.6%, P = 0.03)

Conclusion
Hispanics have a greater risk for presenting with headaches and less peripheral neuropathy than NH. Initiation of outdoor work among H may be the reason of this disproportionate presentation of LD symptoms during spring months. These findings may suggest the propensity for Hispanics to go underdiagnosed with LD, despite their high likelihood of exposure through their occupations in this region.

Disclosures
All authors: No reported disclosures.
Serum and Lung Pharmacokinetics of ASN100, a Monoclonal Antibody Combination for the Prevention and Treatment of Staphylococcus aureus Pneumonia
Authors: Magyarics Zoltan , Leslie Fraser , Luperchio Steven A , Bartko Johann , Schörgenhofer Christian , Schwameis Michael , Derhaschnig Ulla , Lagler Heimo , Stiebellehner Leopold , Jilma Bernd , Stevens Christopher , Nagy Eszter 
Published: October 2017

Abstract

Background
Monoclonal antibodies (mAbs) are well-suited for the prevention and treatment of acute bacterial infections. ASN100 is a combination of two fully human IgG1 mAbs, ASN-1 and ASN-2 that together neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five leukocidins (HlgAB, HlgCB, LukED, LukSF [PVL] and LukGH) that are important in the pathogenesis of S. Aureus pneumonia. We aimed to characterize the pharmacokinetics (PK) of ASN100 in both serum and lung epithelial lining fluid (ELF) in male and female healthy volunteers.

Methods
The safety, tolerability, and serum and lung PK of single intravenous infusion of ASN100 was evaluated in a Phase 1 study. Eight subjects (3:1 randomization) in two double-blind cohorts received ASN100 (doses of 3600 mg or 8000 mg) or placebo. ASN-1 and ASN-2 were administered in a fixed dose 1:1 ratio. Twelve subjects received ASN100 open-label at doses of 3600 mg or 8000 mg and each underwent two bronchoalveolar lavage (BAL) fluid collections either on days 1 and 30 or on days 2 and 8 post-dosing. ASN-1 and ASN-2 concentrations were determined by ELISA. The ELF concentrations were normalized based on urea concentrations in serum and BAL fluid.

Results
No dose limiting toxicity was observed. Adverse events (AEs) showed no association of increased incidence with higher dose. All AEs were mild or moderate in severity, with 83.3% of subjects receiving ASN100 reporting at least one AE vs. 100% of placebo subjects. A dose proportional increase in serum peak and exposure (AUC) of ASN-1 and ASN-2 was observed and the serum PK of ASN-1 and ASN-2 were comparable (approximate half-life of each antibody was 3 weeks). Penetration of ASN-1 and ASN-2 into the ELF of the lung was observed at the first post-dose time point of 24 hours, peak concentrations were observed after day 2 and the mAbs remained detectable at day 30.

Conclusion
ASN100 was safe and well tolerated at doses up to 8000 mg (4000 mg ASN-1 and 4000 mg ASN-2). The PK profiles of ASN-1 and ASN-2 were comparable following simultaneous administration. Significant lung concentrations of each mAb were demonstrated between day 1 and 30 post-dosing. These data support continued clinical development of ASN100 for the prevention and treatment of S. Aureus pneumonia.

Disclosures
Z. Magyarics, Arsanis Biosciences GmbH: Employee, Salary. Arsanis, Inc.: Shareholder, Share options. F. Leslie, Arsanis., Inc.: Employee and Shareholder, Salary. S. A. Luperchio, Arsanis Inc.: Employee and Shareholder, Salary. B. Jilma, Arsanis Biosciences GmbH: Investigator, Investigator fee. C. Stevens, Arsanis Inc.: Employee and Shareholder, Salary.E. Nagy, Arsanis: Employee and Shareholder, Salary.
Comparison of Viral Loads in Patients with Co-infections vs. Single-virus Infections
Authors: Beveridge Stockton , Piya Bhinnata , Stewart Laura , Lindegren Mary Louise , Markus Tiffanie , Schaffner William , Halasa Natasha B 
Published: October 2017

Abstract

Background
Molecular testing for respiratory viruses in clinical practice is common, often with multiple viruses detected. Viral load has been correlated with illness severity, but correlation of co-detection of viruses and viral load is less clear. We sought to compare cycle threshold (Ct) values, a marker inversely related to viral load, between single vs. co-detection of common respiratory viruses.

Methods
Children &lt;18 years with respiratory symptoms and/or fever who presented to the ED or were admitted were enrolled. Nasal/throat specimens were obtained and combined. Singleplex qRT-PCR was used to test for 11 respiratory viruses. Clinical and demographic information were collected.

Results
From 11/15/15-7/15/16, 1255 children were enrolled, with median age of 26.5 months, 53.4% male, 54.3% White, 38.7% Black, 6.4% other, and 23.5% Hispanic. The median days of illness were 3 days. Of the total cohort, 904 (72%) tested positive for at least one viral pathogen. Table 1compares Ct values of single vs. co-detection for each individual virus.

Conclusion
Single detection with RSV, HRV, AdV, and PIV had lower Ct values, indicating higher viral loads, compared with co-detection with other viruses. Additional research is needed to understand the reason for lower viral loads for co-detection vs. single detection in select respiratory viruses.

Disclosures
W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. N. B. Halasa, sanofi pasteur: Research Contractor, Research support. Astra Zeneca: Research Contractor, Grant recipient.