bluuebunny/crossref_metadata_2025_split huggingface dataset:
252. Development and Evaluation of a Novel MultiCode Real-Time PCR Assay for the Detection of Pneumocystis jirovecii in Bronchoalveolar Lavage Fluid and Induced Sputum
Authors: Liu Baoming , Carroll Karen C , Zhang Sean 
Published: October 2019

Abstract

Background
Pneumocystis jirovecii is a medically important fungal pathogen responsible for opportunistic infections in immunocompromised hosts with high morbidity and mortality. Compared with standard microscopy based assays, home-brew nucleic acid amplification tests (NAAT) have emerged as sensitive tools for the diagnosis of P. jirovecii pneumonia, but their sensitivities vary depending upon selected genetic targets. Recent studies suggest that the mitochondrial small subunit (mtSSU) is a better NAAT target given its higher copy number and stable expression in the disease process. We aimed to develop and evaluate a mtSSU-targeted MultiCode real-time PCR assay that incorporates a sample processing control (SPC) and enables detection of P. jirovecii in bronchoalveolar lavage fluid (BALF) and induced sputum.

Methods
Firstly, we compared manual DNA extraction using Zymo Quick DNA kit with automated extraction using the NucliSENS easyMAG system after sample pretreatment with either FastPrep mechanical grinding or vortex-based bead beating. We then determined the mouse hepatitis virus SPC (Luminex) spike-in amount, and optimized the PCR conditions on the ABI 7500 PCR system. A new Pneumocystis mtSSU run control was generated by cloning and transforming mtSSU gene into a genetically engineered E. coli strain, and quantified with a home-brew quantitative TaqMan PCR. Lastly, the performance characteristics of the MultiCode PCR assay were determined.

Results
Mechanical grinding of BALF or sputum before the easyMAG based extraction was better than the other extraction protocols as evidenced by lower CT of mtSSU or SPC. Diluted SPC added to samples before DNA extraction made its CT within 31–34. With the mtSSU run control, the limit of detection of the new assay was 80 copies/mL. No cross-reactivity was found with 9 respiratory viruses, 8 bacteria or 11 fungi. The assay has high reproducibility for three-day detection of the same sample aliquots for mtSSU (CT: 30.0–30.3; CV%: 0.5–1.6) and SPC (CT: 32.1–32.2; CV%: 0.8–2.4).

Conclusion
We developed a novel MultiCode real-time PCR assay for detection of P. jirovecii in BALF and sputum, which demonstrated high analytical sensitivity, specificity and reproducibility and warrants further clinical validation.

Disclosures
All authors: No reported disclosures.
253. Evaluation of a Cryptococcal Antigen Lateral Flow Assay and the Burden of Cryptococcal Disease: A Cohort Study at Grady Memorial Hospital in Atlanta, Georgia
Authors: Harrington Kristin , Wang Yun , Rebolledo Paulina , Liu Zhiyong , Yang Qianting , Kempker Russell R 
Published: October 2019

Abstract

Background
While Cryptococcus neoformans is a major cause of morbidity and mortality among HIV-infected persons worldwide, there is scarce recent data on disease prevalence in the United States, including in Southeastern states, where HIV rates are high. We sought to determine the prevalence of cryptococcal disease and compare the performance of a cryptococcal antigen (CrAg) lateral flow assay (LFA) vs. latex agglutination (LA) test.

Methods
All patients from Grady Memorial Hospital in Atlanta, Georgia who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg LA testing as part of routine management from November 2017 to July 2018 were included. The LFA was performed on all samples by research staff; results were not available to clinicians. Rates of disease and agreement between the LA test and LFA were calculated.

Results
Among 467 patients, 570 LA tests were performed; 417 on serum and 153 on CSF (87 patients with multiple tests performed). Mean age was 44 years, and most were male (n = 322, 69%). Most patients had HIV (n = 371, 79%); median CD4 count was 73 cells/mm3 and 77% were not receiving ART. Among HIV-infected individuals, testing was performed equally in the inpatient and outpatient setting. Cryptococcal testing was done in 53 persons without apparent risk factors. Thirty-three (7%) patients had a positive serum or CSF test. Five (1%) patients had both a positive serum and CSF LA test and LFA. While the overall agreement between the LA test and LFA was substantial to high for CSF (κ = 0.71) and serum (κ = 0.93), respectively, there were important discrepancies. Four patients with a negative serum LA test had a positive serum LFA. Five patients had false-positive CSF LA tests, determined by negative CSF LFA testing, India ink, and CSF and fungal cultures. All were treated with amphotericin and flucytosine with one patient experiencing a severe anaphylactic reaction to amphotericin.

Conclusion
We found a moderately high rate of cryptococcal disease and important discrepancies between the LA test and LFA. The LFA appeared to be more sensitive for cryptococcemia and more specific for meningitis. Clinical implications of these findings include earlier detection and treatment of cryptococcemia, and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.

Disclosures
All authors: No reported disclosures.
259. Racial Differences in Clinical Phenotype and Hospitalization of Blastomycosis Patients
Authors: Anderson Jennifer L , Frost Holly M , King Jennifer P , Meece Jennifer K 
Published: October 2019

Abstract

Background
Dimorphic fungal infections, such as blastomycosis, cause significant morbidity and mortality. Most studies describing blastomycosis have focused on non-Hispanic Caucasians and our understanding of the clinical presentation and outcomes for patients of other race/ethnicities is limited. We evaluated whether clinical presentation and disease severity varied across racial/ethnic groups.

Methods
Blastomycosis patients were identified from Marshfield Clinic Health System and patient data were abstracted from electronic medical records. Blastomyces genotyping was performed for cases with available isolates. Univariate analyses using χ 2 tests and multivariate logistic regression modeling were used to determine the association of race/ethnicity with clinical presentation. Significance was defined as P ≤ 0.05.

Results
In total 477 patients were included.Age differences were observed across race/ethnicity categories (P < 0.0001). Non-Hispanic, Caucasians were oldest (47 years, SD 20) and Asians were the youngest (30 years, SD 18). Underlying medical conditions were more common in non-Hispanic Caucasians (55%) and African Americans (AA) (52%) than Hispanic Caucasians (27%) and Asians (29%, P = 0.0002). Risk for hospitalization was highest for Hispanic Caucasian (aOR 2.9, 95% CI 1.2–1.7), American Indian Alaskan Native (AIAN) (aOR = 2.4; 95% CI 1.0–5.5), and Asian (aOR = 1.9; 95% CI 1.0–3.6) patients when compared with non-Hispanic Caucasian patients. Ninety percent of B. dermatitidis infections occurred in non-Hispanic Caucasians whereas blastomycosis in Hispanic Caucasian, AIAN, and Asian patients was frequently caused by B. gilchristii (P < 0.0001).

Conclusion
Hispanic Caucasian, AIAN, and Asian blastomycosis patients were younger and healthier, but more frequently hospitalized. Patients in these racial/ethnic groups may need more aggressive treatment and closer therapeutic monitoring. Underlying host factors along with organism virulence likely play a role in these differences.

Disclosures
All authors: No reported disclosures.
276. Detection of Rhizopus oryzae-Specific Antigen (RSA) in Serum and Bronchial Alveolar Lavage Is a Potential Early Diagnostic Marker in Mucormycosis by R. oryzae
Authors: Shibata Wataru , Yamada Koichi , Niki Mamiko , Yamagoe Satoshi , Miyazaki Yoshitsugu , Kaneko Yukihiro , Kakeya Hiroshi 
Published: October 2019

Abstract

Background
The diagnosis of mucormycosis was made by the identification of an organism in the histopathology with culture confirmation. However, culture often yields no growth, and histopathological identification of organism with typical of mucorales is sometimes difficult. Therefore, a reliable new diagnostic tool is expected. We reported a novel Rhisopus-specific antigen (23kDa, named protein RSA) by screening with a signal sequence trap was detected at significantly higher concentrations in serum and in lung homogenates in the infected mice on day 4. And the results were suggested RSA was a possible diagnostic marker of mucormycosis (Sato K, et al. Medical Mycology, 2017, 55,713–719). Here, we examined whether the RSA was detected on early stage in sera and bronchial alveolar lavage (BAL) of infected mice.

Methods
We developed the ELISA Kit using monoclonal antibody for RSA. The mice were injected with cortisone acetate and cyclophosphamide, and R. oryzae was infected intratracheally. Mice sera and BAL was obtained from infected mice on day 1, 2, 3, and 4. Then the concentration of RSA in sera and BAL was evaluated using the ELISA Kit for RSA.

Results
The RSA was detected in sera and BAL on day 1, 2, 3, and 4. The concentration of RSA in sera and BAL were significantly higher on day 1 as compared with uninfected mice. And the concentration of RSA in sera was the upward trend through day 1 to 4. However, the concentration of RSA in BAL was stable through day 1 to 4.

Conclusion
The RSA is a potential early diagnostic marker in mucormycosis by R. oryzae.

Disclosures
All authors: No reported disclosures.
291. Using Individualized Provider Feedback to Improve HCV Screening in a High-Volume Emergency Department
Authors: Zucker Jason , Sani Fereshteh , Ruperto Kenneth , Slowkowski Jacek , Purpura Lawrence , Schluger Aaron , Olender Susan , Scherer Matt , Gordon Peter 
Published: October 2019

Abstract

Background
Ending the Hepatitis C Virus (HCV) epidemic requires HCV testing as the critical first step. Busy urban Emergency Rooms are uniquely suited for HCV screening programs but numerous barriers to effective program implementation exist. We describe an emergency room physician champion model that utilizes the feedback intervention theory (FIT) to providers to increase HCV screening rates.

Methods
Due to the changing epidemiology of HCV in 2017 New York Presbyterian supported one-time universal HCV screening. In September 2018, our physician champion provided an educational session to ED providers about the importance of HCV screening and the proposed study. From the end of September to the end of March 2019, providers received a monthly e-mail from the ED champion and an automated text message with their individual and peer HCV screening rates. The number of HCV tests and percent of individuals with documented HCV testing in the ED was compared pre and post this intervention and to HCV testing in the inpatient and outpatient setting where feedback was not provided.

Results
On average ED providers evaluated approximately 14,000 patients per month. HCV testing increased 1,600% from an average of 40 tests per month in the 18 months prior to the intervention to an average of 640 tests sent per month during the intervention. tests sent in December. This was compared with stable inpatient and outpatient HCV screening during the same time period.

Conclusion
Individualized provider feedback paired with an ED physician champion can lead to a significant increase in HCV testing. Ongoing studies will determine if this intervention can lead to long-term behavior change.

Disclosures
All authors: No reported disclosures.
293. Hepatitis C is now a Millennial Disease in Response to the Opioid Crisis: A Demographic Shift in Hepatitis C Infection
Authors: Rose Michelle , Allen Myers John , Ryan Nicholas , Prince Alissa , Talbot Morgan , Espinosa Claudia M 
Published: October 2019

Abstract

Background
Previous research has shown millennials represent the fastest growing generation for those infected with the hepatitis C virus (HCV). Millennials are also a key driver in the opioid crisis, particularly in states of the Appalachian region including Kentucky. Despite research demonstrating a change in prevalence from baby boomers (born 1945–1965) to millennials (born 1980–1995), large representative studies providing evidence of the magnitude of this demographic shift are lacking in the United States. Our objective was to assess trends of HCV infection since 2016 in a large healthcare system located in an area of high prevalence of opioid use and HCV infection.

Methods
All individuals were screened for HCV infection in 2016, 2017, and 2018 within Norton Healthcare per standard risk-based criteria (e.g., injection drug users, baby boomers, etc.) as recommended by CDC, except for pregnant women who were universally screened since 2016. We tested for demographic shifts over time using longitudinal and time series analyses techniques

Results
A total of 86,243 individuals were screened for HCV infection from 2016 to 2018. Of those, 2,615 (3.0%) individuals screened positive for chronic HCV. The average age of those infected significantly decreased by an average of 3.7 years annually (from 47.3 years in 2016 to 39.9 years in 2018, P < 0.001). We forecast a plateau near the age of 28 years will be observed in just over 7 years. In addition, the proportion of millennials increased over time (33.6% in 2016, 42.4% in 2017 and 51.4% in 2018, P < 0.001), while baby boomers significantly decreased over time (44.0% in 2016, 38.8% in 2017, and 29.3% in 2018, P < 0.001). Lastly, over time, those with chronic HCV were more likely to be male (increasing from 49.6% to 54.4%, P = 0.008) and Hispanic (increasing from 1.6% to 17.7%, P < 0.001)

Conclusion
Our results suggest that HCV infection has become a predominately millennial disease, skipping a generation. These results correlate with trends seen with the opioid epidemic, which is driven by millennials. We conclude that the opioid crisis has led to a drastic demographic shift, and currently the typical HCV-infected individual is a younger male. Without interventions, this trend will continue for over seven years, plateauing near the demarcation of millennials and generation Z

Disclosures
All authors: No reported disclosures.
307. Overcoming Hepatitis C Elimination Challenges in the Coachella Valley through the Collaboration of Linkage to Care, a Managed Care Organization, and a Federally Qualified Health Center
Authors: Duong Nicolette , Valenzuela Lindsey , Singh Tulika , Morris David , Hodgkins Brian , Le Jade , Kerkar Shubha J 
Published: October 2019

Abstract

Background
Per the Centers for Disease Control and Prevention, 2.4 million Americans have the hepatitis C virus (HCV). New cases increased by 14% from 2014 to 2016 in California with 400,000 infections, 4,000 infections in the Coachella Valley and about 50% unaware of their diagnosis. A barrier to elimination is the lack of rapid screenings and linkage to care (LTC) of infected individuals into an integrated system. Thus, we developed a program at the Hepatitis Center of Excellence (HCE) where pharmacists in a managed care organization (MCO) provide opportunities to overcome these boundaries. The partnership of the MCO and federally qualified health center (FQHC) was established in 2017 to expand access to care to the HCV community. We anticipate that our program will eliminate HCV in the Coachella Valley by modeling past success in human immunodeficiency virus (HIV) testing and LTC at the FQHC through an interdisciplinary approach.

Methods
A single-center, retrospective analysis from January 2017 to December 2018 of HCV individuals was conducted at the pharmacist-led HCE in Palm Springs, California. The LTC team approached barriers through prompt free screenings and major advocacy. Pharmacists and specialty physicians collaborated to ensure rapid assessment, treatment initiation and completion, and sustained virologic response (SVR). The HCE has adapted the HIV testing and LTC model in hopes of achieving similar feats. From 2014 to 2018, 92,947 total HIV tests were performed with 90.2% of HIV-positive patients linked to care. HCV testing was then added to HIV screening and expanded to other testing sites.

Results
The first visit with a clinical pharmacist consists of education, reviewing lab tests, cost assistance, and providing treatment options. From 2017 to 2018, 169 of 172 HCV positive individuals (98.2%) achieved SVR by treatment completion. The HCV LTC program demonstrated a 3.8% increase in HCV testing from 2017 to 2018.

Conclusion
Pharmacist-led care for a large volume of HCV patients allows time for specialty physicians to manage more complex cases. The collaboration between the FQHC, MCO, and LTC team showed HCV elimination is possible based on high SVR rates. HCE is projecting successful linkages to care and continuous campaigning for individuals to be treated for HCV in the Coachella Valley.

Disclosures
All authors: No reported disclosures.
310. Disparities in Hepatitis C Linkage to Care in the DAA Era: Findings from a Referral Clinic with an Embedded Nurse Navigator Model
Authors: Sherbuk Jacqueline , McManus Kathleen , Knick Terry , Dillingham Rebecca 
Published: October 2019

Abstract

Background
Direct-acting antivirals (DAAs) have simplified and expanded access to Hepatitis C virus (HCV) treatment. Only 17% of the estimated 2.4 million Americans currently infected with HCV have linked to HCV specialty care. We evaluated linkage to care (LTC) in a non-urban hepatitis C referral clinic with a nurse navigator model of care and identified disparities in LTC during the DAA era.

Methods
A single-center retrospective cohort analysis was performed among all patients referred to an infectious diseases HCV clinic between 2014 and 2018. The primary outcome was LTC, defined as attendance at a clinic appointment. A multivariable Poisson regression model estimated associations of patient characteristics with LTC.

Results
Among 824 referred patients, 624 (76%) successfully linked to care and 369 (45%) achieved sustained virologic response. The mean age was 48.5 years (SD 13.5 years) and 46% (382 of 824) were uninsured. Common reasons for failure of LTC included no-shows (26.5%), could not be contacted (20.5%) and incarceration (10%). On multivariable analysis, LTC rates were higher among women (incidence rate ratio (IRR) 1.11, 95% CI 1.03–1.20, P = 0.01) and those with cirrhosis (IRR 1.20, 95% CI 1.11–1.30, P < 0.001). Lower rates of LTC were seen for young people (< 40 years old) (IRR 0.88, 95% CI 0.79–0.98, P = 0.02) and uninsured people (IRR 0.85, 95% CI 0.77–0.94, P = 0.002). Race, proximity to care, substance use, and HIV status were not associated with differences in LTC rates.

Conclusion
In an embedded nurse navigator model of care, a high rate of LTC was achieved despite the prevalence of barriers, including a high uninsured rate. LTC was the biggest drop-off in the cascade. Disparities in LTC based on age, sex, and insurance status are present. Substance use was not associated with differences in LTC, supporting current recommendations to provide treatment to all patients with HCV. No-shows were common, potentially due to lack of reliable contact information or lack of transportation. Qualitative work exploring patients’ experiences leading to failure of LTC would be helpful. Future interventions to improve care could include expanded access to insurance, affordable medical tests, and programs bridging care for incarcerated populations.

Disclosures
All authors: No reported disclosures.
331. Five Cases of Hemophagocytic Lymphohistiocytosis in Patients with HIV: A Fulminant and Lethal Combination
Authors: Bhatt Isha , Khan Zeb , Lam Paul , Quale John M 
Published: October 2019

Abstract

Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that can be either primary (genetic) or secondary (reactive) in etiology. Diagnosis can be elusive, especially in patients with HIV infection.

Methods
Medical records were reviewed for 5 patients with HIV infection and the diagnosis of HLH. Standard and alternative criteria were utilized to establish the diagnosis.

Results
Five patients with HIV infection had clinical criteria for the diagnosis of HLH. Ages ranged from 33–70 years and 4 were males. All five presented with fevers, cytopenias, and markedly elevated ferritin levels (table). All of the patients had CD4 levels of < 200 cells/µL. Evidence of hemophagocytosis was found on bone marrow examination in 3 patients. Inciting conditions included Pneumocystis jiroveci infection, EBV infection, lymphoma, and multiple myeloma. All patients received broad-spectrum antimicrobial as well as immunosuppressive therapy. Despite aggressive treatments, all patients died within one month of presentation.

Conclusion
In patients with underlying HIV infection, HLH can be a difficult diagnosis to establish. Mortality rates can be high, even with prompt recognition and therapy. The finding of fever and cytopenia in a patient with HIV infection should prompt the clinician to determine a ferritin level. If markedly elevated, the diagnosis of HLH should be aggressively pursued.

Disclosures
All authors: No reported disclosures.
337. Switching from TDF to TAF: Missed Opportunities for Statin Use in HIV
Authors: Mallon Patrick , Brunet Laurence , Fusco Jennifer S , Prajapati Girish , Beyer Andrew P , Wohlfeiler Michael , Fusco Gregory 
Published: October 2019

Abstract

Background
People living with HIV (PLWH) have been observed to have twice the risk for atherosclerotic cardiovascular disease (ASCVD) as the general population. Increases in total and low-density lipoprotein cholesterol have been observed in PLWH switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Changes in regimens represent an opportunity for healthcare providers to assess health markers and address clinical concerns. Current guidelines recommend initiating statin therapy in individuals with an elevated ASCVD risk. Failure to initiate statins in PLWH with an ASCVD ≥ 7.5% at switch represents a missed opportunity for statin initiation. We aimed to assess missed opportunities for statin therapy in PLWH switching from TDF to TAF-containing antiretroviral therapy.

Methods
Adults switching from TDF to TAF with ≥1 lipid measure on TDF ≤6 months prior to switch and ≥1 lipid measure ≥7 days after switch to TAF were identified in the OPERA® cohort (84 clinics in 18 US states/territories). The proportion of PLWH prescribed statins pre- and post-switch was stratified by ASCVD risk (recommended threshold: ASCVD ≥ 7.5%). The ASCVD score was imputed using the limit value for components out of the pre-specified range.

Results
6,451 PLWH switched from TDF to TAF (Figure 1); over 90% had ASCVD scores available pre- (n = 5801) and post-switch (n = 5881). High ASCVD risk (≥7.5%) was more likely post-switch (34.1) than pre-switch (32.1%, P = 0.02; Figure 2). Of those with high ASCVD risk, only 31% and 41% were prescribed statins pre- vs. post-switch, respectively (Figure 3), representing a considerable missed opportunity for ASCVD prevention, with 59% of PLWH with an elevated risk of ASCVD not prescribed statins after switch from TDF to TAF. ASCVD scores were imputed for those outside the range of the score (e.g., patients < 40 years of age) to evaluate the entire population. Comparable results were obtained when the analysis was limited to PLWH who did not require ASCVD score imputation.

Conclusion
Despite a switch from TDF to TAF being associated with higher numbers of PLWH with elevated ASCVD risk, most did not receive a statin, representing considerable missed opportunities to reduce risk of cardiovascular disease in this at-risk population.

Disclosures
All authors: No reported disclosures.