bluuebunny/crossref_metadata_2025_split huggingface dataset:
976. Development and Validation of a Risk Score for Predicting Cardiovascular Events in HIV-Infected Patients
Authors: Karanika Styliani , Karantanos Theodoros , Carneiro Herman , Assoumou Sabrina A 
Published: October 2019

Abstract

Background
HIV-infected individuals are at higher risk for developing cardiovascular disease (CVD). We aimed to develop a model to predict 10-year cardiovascular (CV) risk given that commonly used CVD risk assessment tools might not be accurate for HIV-infected patients.

Methods
We conducted a retrospective cohort study of HIV-infected patients seen at Boston Medical Center between March 2012 and January 2017. Exclusion criteria are shown in Figure 1. Patients were divided into model development and validation cohorts. Logistic regression was used to create a risk model for CV events using data from the development cohort. The relationship between risk factors and CVD risk was summarized using a point-based risk-scoring system. Areas under the receiver-operating-characteristics curve (AUC) were used to evaluate model discrimination. The model was subsequently tested using the validation cohort.

Results
Of 3,867 eligible HIV-infected patients, 1,914 individuals met inclusion criteria (Figure 1). There were 256 CV events in the development cohort. Ten independent prognostic factors were incorporated into the prediction function (Pmodel < 0.001). The model had excellent discrimination for CVD risk [AUC 0.94; (95% CI:0.93–0.96)] (Figure 2) and included the following variables: male sex (P < 0.001), African-American ethnicity (P = 0.023), current age (P = 0.020), age at HIV diagnosis (P = 0.006), peak HIV viral load (P = 0.012), nadir CD4 lymphocyte count (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P = 0.001), diabetes (P < 0.001), and chronic kidney disease (P < 0.001). Scoring system and score sheets of risk estimates were developed to predict CV events in a 10-year follow-up period (Figures 3 and 4). The 10-parameter multiple logistic regression model also had excellent discrimination [AUC 0.96; (95% CI: 0.89–0.99)] when applied to the validation cohort.

Conclusion
We developed and validated a risk-scoring system based on 10 clinical factors that accurately predict the 10-year risk for CV events in an HIV-infected population. This assessment tool may provide clinicians with a rapid assessment of cardiovascular disease risk among HIV-infected patients and inform prevention measures during the era of effective antiretroviral therapy.

Disclosures
All Authors: No reported Disclosures.
977. The Prevalence and Burden of Non-AIDS Co-Morbidities in Women with or At-risk for HIV Infection in the United States
Authors: Collins Lauren F , Sheth Anandi N , Mehta C Christina , Golub Elizabeth T , Tien Phyllis C , Anastos Kathryn , French Audrey L , Kassaye Seble , Taylor Tonya , Kempf Mirjam-Colette , Fischl Margaret A , Adimora Adaora A , Palella Frank J , Ofotokun Igho 
Published: October 2019

Abstract

Background
Age-related non-AIDS comorbidities (NACM) increasingly account for morbidity and mortality in persons living with HIV. The burden of NACM and its association with HIV is poorly described in women.

Methods
We analyzed data from HIV+ and at-risk HIV− participants who were followed in the Women’s Interagency HIV Study (WIHS) after 2009 (when >80% of participants used antiretroviral therapy). The prevalence of each NACM (defined by a combination of self-report, clinical measurements, and laboratory data) and the number of NACM were summarized at a most recent follow-up visit and were compared by age and HIV serostatus using unadjusted linear regression models.

Results
There were 3232 women (2309 HIV+, 923 HIV–) with a median follow-up of 15.3 years. The median age was 50 years, 65% were black, 38% currently smoked, 71% had ever used illicit drugs, 50% had annual income < $12,000, and median body mass index was 30 kg/m2. HIV+ women had a median CD4 count of 618 cells/mm3 and 66% had HIV viral suppression. Among 10 NACM evaluated, the following were more prevalent in HIV+ vs. HIV– women (all P < 0.01): psychiatric illness (57%/48%), liver disease (45%/26%), hyperlipidemia (40%/35%), bone disease (40%/33%), chronic kidney disease (15%/7%), and non-AIDS cancer (11%/7%). There was little difference in the prevalence of hypertension (66%/64%), lung disease (41%/43%), diabetes (22%/24%), and cardiovascular disease (19%/19%). Mean number of NACM was higher in HIV+ vs. HIV– women (3.6 vs. 3.0, P < 0.0001). Regardless of HIV serostatus, NACM burden significantly increased with age (P < 0.0001). Compared with women aged <40 of the same HIV serostatus, the estimated mean difference in NACM (HIV+/HIV–) for those 40–49, 50–59, ≥60 years was 1.1/0.7, 2.3/2.3, and 3.6/3.2, respectively (P < 0.0001 for all). Within-age-group comparisons revealed significantly greater NACM burden in HIV+ vs. HIV− women aged 40–49 years (P < 0.0001) and ≥60 years (P = 0.003), but not in those aged <40 or 50–59 years (HIV*age interaction P = 0.02) (figure).

Conclusion
NACM burden was high in both HIV+ and at-risk HIV– women, but higher in HIV+ women overall and in certain age groups. Accumulation of NACM has complex implications for clinical care, medication management, and healthcare screening that must be further examined in this population.

Disclosures
Anandi N. Sheth, MD, MS, Gilead Sciences, Inc.: Research Grant.
1824. Herpes Simplex Encephalitis: Outcomes from a 10-Year Retrospective Single-Center Case Series
Authors: Snider Christina A , Banzon Jona , Bhimraj Adarsh , Procop Gary W , Goldfarb Johanna 
Published: October 2019

Abstract

Background
Herpes simplex virus (HSV) is the most common cause of infectious encephalitis in the United States. While early treatment with acyclovir has improved acute management, long-term morbidity and mortality remain high and warrant further characterization.

Methods
We retrospectively identified adult patients (≥18 years) with HSE admitted to the Cleveland Clinic Main Campus and affiliated regional hospitals from April 2006 to June 2016. HSE diagnosis was concordant with Infectious Disease Society of America Encephalitis Guidelines. HSE diagnosis was confirmed in that HSV-1 DNA was detected in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) assay for all patients included in this study. Patients for which HSV-2 was detected in the CSF were excluded to avoid inclusion of HSV meningitis. Clinical information was collected in a REDCap database and analyzed by descriptive statistics. Patients were indexed at the date of admission, and Kaplan–Meier analysis was used to estimate overall survival.

Results
We identified 32 patients with confirmed HSE. The median patient age was 62 years (interquartile range [IQR] 45–72). All patients received treatment with intravenous (IV) acyclovir, with a median treatment duration of 24 days (IQR 19–30). The median time from initial symptom onset to IV acyclovir treatment was 5 days (IQR 3–8). Three patients (9%) died during the hospitalization course, 16 (50%) were discharged to a nursing facility, 11 (35%) returned home, and two (6%) transitioned to an acute care facility (Figure 1). Within three months of discharge, 15 (47%) patients were readmitted, six (19%) of which readmitted for HSE relapse. The overall survival rate at one month was 84% and 74% at 12 months (Figure 2). At outpatient follow-up, cognitive deficits were self-reported by 19 (66%) patients, followed in frequency by motor (31%) and sensory deficits (7%).

Conclusion
Despite appropriate treatment with IV acyclovir, HSE survivors frequently experienced severe morbidities after initial hospitalization, including HSE relapse, discharge to long-term care facilities, and neurocognitive impairment. Risk of death was highest within one month of admission. Further investigation is needed to optimize treatment of HSE to improve mortality and to reduce permanent neurologic deficits.

Disclosures
All Authors: No reported Disclosures.
1835. High Burden of Invasive Staphylococcus aureus Disease Among Native Americans on the White Mountain Apache Tribal Lands
Authors: Sutcliffe Catherine , Grant Lindsay , Reid Angelina , Douglass Grace K , Brown Laura B , Kellywood Kamellia , Weatherholtz Robert , Hubler Robin , Quintana Alvaro , Close Ryan M , McAuley James , Santosham Mathuram , O’Brien Katherine , Hammitt Laura 
Published: October 2019

Abstract

Background
Native Americans in the southwestern United States (US) have a higher risk of many infectious diseases than the general US population. The objective of this study was to determine the burden of invasive Staphylococcus aureus disease among Native Americans on the White Mountain Apache (WMA) Tribal lands.

Methods
Prospective population and laboratory-based surveillance for invasive S. aureus infections was conducted from May 2016 through April 2018. A case was defined as a Native American individual living on or around the WMA Tribal lands with S. aureus isolated from a normally sterile site. Incidence rates were calculated using the Indian Health Service User Population as the denominator. Age-standardized incidence rates were calculated by direct standardization methods using US Census data from 2015 as the reference.

Results
Fifty-three cases were identified (Year 1: 24; Year 2: 29). Most cases were adults (90.6%; median age: 47.4 years) and had ≥1 underlying medical condition (86.8%), of which the most common were obesity (50.0%) and diabetes (50.0%). 26.4% of cases were categorized as community acquired. Most infections were methicillin-resistant (MRSA; 75.5%). 88.7% of cases were hospitalized, 7.5% required amputation, and 7.7% died within 30 days of the initial culture. The overall incidence of invasive S. aureus was 156.3 per 100,000 persons (95% confidence interval [CI]: 119.4, 204.5) with no significant difference in the incidence by year (Year 1: 141.5; Year 2: 171.1; incidence rate ratio: 1.21; 95% CI: 0.70, 2.08). The overall incidence of invasive MRSA was 118.0 per 100,000 persons (95% CI: 86.5, 160.8) with no significant difference by year (Year 1: 106.1; Year 2: 129.8; incidence rate ratio: 1.22; 95% CI: 0.66, 2.28). The incidence of invasive S. aureus and MRSA increased with age and was highest among individuals 50–64 years of age. The overall age-adjusted incidence of invasive MRSA was 138.2 per 100,000 persons (Year 1: 125.2; Year 2: 150.9, for comparison US 2015 general population: 18.8 per 100,000 persons).

Conclusion
The WMA community has one of the highest reported incidence rates globally of invasive MRSA. Interventions are urgently needed in this community to reduce the morbidity and mortality associated with these infections.

Disclosures
All Authors: No reported Disclosures.
1872. Neurodevelopment in Apparently Normal Infants from Zika Virus Positive Pregnancies
Authors: Mulkey Sarah B , Arroyave-Wessel Margarita , Peyton Colleen , Bulas Dorothy , Vezina Gilbert , Fourzali Yamil , Morales Armando , Swisher Christopher , Cristante Caitie , Russo Stephanie , Kousa Youssef , Jiang Jiji , Msall Michael , McCarter Robert , du Plessis Adre , Cure Carlos , DeBiasi Roberta 
Published: October 2019

Abstract

Background
Congenital Zika syndrome (CZS) is seen in 5–12% of newborns from Zika virus (ZIKV)-infected pregnancies and includes severe neurologic abnormalities. However, the majority of ZIKV-exposed newborns do not have CZS. The risk for neurodevelopmental impairment for infants without CZS following in utero ZIKV is not well known. The objective was to determine whether infants without CZS exposed to ZIKV in utero, have normal neurodevelopment.

Methods
We performed a longitudinal study of neurodevelopment in Colombia for infants exposed to ZIKV in utero who had a normal fetal brain MRI (Mulkey et al, JAMA Peds 2019) and normal head circumference at birth. Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) between 6 and 18 months of age. In-person training was done by a neurologist. The AIMS were video-recorded and scored centrally. Interrater reliability for the novel method of video-based AIMS was determined. WIDEA and AIMS scores were converted to Z-scores compared with normative samples. We also compared development between infants with normal and nonspecific findings on cranial ultrasound (US).

Results
Seventy-two non-CZS infants had neurodevelopmental tests; 40 were at a mean (SD) of 5.7 (0.9) months and 66 were at 13.5 (3.2) months of age. Thirty-four had two assessments. The total WIDEA, social cognition, and mobility domain scores became more abnormal with postnatal age (figure). The AIMS scores were similar to the normative sample. Three infants had an AIMS score < 2 SD’s below the norm. On cranial US, 19 infants (26%) had a nonspecific finding (lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts, and/or calcification). Infants with a US finding had a lower WIDEA mobility score than infants with normal US (P = .054). There was a trend toward lower AIMS scores in infants with US findings compared with infants with normal US (P = .26). AIMS Interrater agreement on video-based scoring was good (ICC = 0.73, 95% CI 0.42, 0.87).

Conclusion
ZIKV-exposed infants without CZS are at risk for neurodevelopmental delay. Nonspecific cranial US findings may represent mild ZIKV-related injury. Long-term neurodevelopmental follow-up is important for all ZIKV-exposed infants.

Disclosures
All Authors: No reported Disclosures.
1881. The Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use: Results From a National Antibiotic Stewardship Intervention of 402 United States (US) Hospitals
Authors: Tamma Pranita , Tamma Pranita , Miller Melissa A , Dullabh Prashila , Ahn Roy , Speck Kathleen , Gao Yue , Cosgrove Sara E , Cosgrove Sara E 
Published: October 2019

Abstract

Background
The AHRQ Safety Program for Improving Antibiotic Use aims to improve antibiotic (abx) use in acute, long-term, and outpatient care settings by enhancing abx stewardship programs (ASP) and engaging frontline providers to incorporate stewardship into daily abx decision-making, with an emphasis on viewing appropriate prescribing as a patient safety issue. We report on the impact of implementation of the Acute Care Safety Program on abx use and Clostridioides difficile in a cohort of US hospitals.

Methods
The Acute Care Safety Program was implemented from December 2017 to November 2018. At least one unit from each hospital participated. The Safety Program trained local ASP leaders and assisted ASPs and frontline staff to: (a) address attitudes and culture that pose challenges to judicious abx use and (b) incorporate best practices for the management of common infections into daily practice using the Four Moments of Antibiotic Decision Making framework (Figure 1). Education occurred via 17 live Webinars and an online toolkit that included recorded Webinars, narrated presentations, and other tools to assist with the development and dissemination of syndrome-specific local guidelines (Table 1). Units submitted days of abx therapy (DOT) per 1,000 patient-days (PD), C. difficile LabID events per 10,000 PD, and 10 review forms per month documenting structured discussions between the ASP and frontline staff about patients on abx. Linear and generalized linear mixed-effects models were employed to calculate pre-post intervention changes in abx use and C. difficile LabID events, respectively.

Results
402 hospitals completed the Safety Program, including 28 (7%) academic medical centers (AMC), 289 (72%) community hospitals, and 85 (21%) critical access hospitals. 476 participating units consisted of 165 (35%) ICUs, 300 (63%) medical-surgical floors, and 11 (2%) other units. Both abx use and C. difficile LabID events decreased when comparing pre-post data (−41 DOT per 1,000 PD, [from 886.56, Figure 2], P = 0.001 and −1.2 LabID events per 10,000 PD [from 6.3], P = 0.027), respectively.

Conclusion
By targeting both improving abx prescribing culture and knowledge of best practices, the AHRQ Safety Program led to reductions in abx use across a diverse cohort of hospitals.

Disclosures
Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.
1884. Clinical Outcomes Among Patients with Drug-Resistant Tuberculosis Receiving Bedaquiline or Delamanid Containing Regimens
Authors: Kempker Russell R , Mikiashvili Lali , Zhao Yuan , Benkeser David , Barbakadze Ketino , Bablishvili Nino , Peloquin Charles , Blumberg Henry , Kipiani Maia 
Published: October 2019

Abstract

Background
Bedaquiline and delamanid are new and much-needed treatment options for drug-resistant tuberculosis (TB); however, there are limited data guiding their use and no direct comparison of the two drugs. We thus sought to compare the clinical outcomes of patients with drug-resistant tuberculosis receiving either a bedaquiline- or delamanid-based treatment regimen.

Methods
This is a prospective observational study among patients with drug-resistant pulmonary TB in the country of Georgia from 2015 to 2017. Patients receiving bedaquiline or delamanid were eligible to be enrolled. Monthly sputum cultures and MIC testing on Mycobacterium tuberculosis isolates were performed. Clinical outcomes included time to culture conversion, rate of acquired drug resistance and treatment outcomes.

Results
Among 156 patients with MDR-TB who were approached, 100 were enrolled, and 95 were receiving a bedaquiline (n = 64) or delamanid (n = 31) based regimen and included in the study. Patients receiving bedaquiline or delamanid were similar with regards to age, BMI, substance use, comorbidities, rate of cavitary disease, and extensively drug-resistant (XDR) TB. Rates of additional Class A drug use including linezolid (78 vs. 81%) and a fluoroquinolone (39 vs. 36%) were similar and the mean effective drugs received per group was 4 (IQR 3–4, P = 0.33). Median drug duration was 171 days for bedaquiline and 182 days for delamanid; no patient discontinued due to QTC prolongation. Adjusted cumulative culture conversion rates at 60 days (64% vs. 48%, P = 0.14) and 180 days (95% vs. 77%, P = 0.02) were higher in patients receiving bedaquiline compared with delamanid (see figure). Rates of acquired drug resistance were higher in patients receiving delamanid compared with bedaquiline (35 vs. 12%, P < 0.01). Lastly, patients receiving a bedaquiline-based regimen had higher rates of favorable outcomes as compared with patients receiving delamanid (94% vs. 67%, P < 0.01).

Conclusion
Patients receiving bedaquiline- and delamanid-based treatment regimens for drug-resistant TB had similar characteristics and those receiving bedaquiline had better clinical outcomes. Our results provide an important first comparison of bedaquiline vs. delamanid containing regimens.

Disclosures
All Authors: No reported Disclosures.
1885. T-helper 1 (Th1) Production of Interferon Gamma (IFNγ) Is Directly Inhibited by TGFβ Within Pulmonary Mycobacterium tuberculous (Mtb) Granulomas
Authors: Gern Benjamin H , Adams Kristin , Stoltzfus Caleb , Plumlee Courtney , Gerner Michael , Urdahl Kevin 
Published: October 2019

Abstract

Background
CD4 T-cell production of IFNɣ is essential to prevent dissemination of pulmonary Mtb, though is less effective at controlling infection within the lung. Because T cells are most effective in the context of direct interactions with Mtb-infected cells, we sought to determine the location of CD4 T-cell antigen sensing and IFNɣ production within granulomas.

Methods
We used a murine ultra-low-dose aerosol infection, developed by our lab, where most mice are infected by a single bacillus, resulting in a solitary granuloma that is more similar to human granulomas. We examined the lungs of wild-type mice 35 days later for patterns of T-cell activation with quantitative confocal imaging. This analysis was next performed following adoptive co-transfer of Th1 polarized Mtb-specific cells and control cells of irrelevant specificity (OVA). To determine the effect of TGFβ on IFNɣ production, we examined mice that lack the TGFβR on T cells (TGFβR.KO). Finally, we examined whether this effect was Th1 cell-intrinsic with an adoptive transfer of Th1-polarized Mtb-specific cells with (Tg.WT) and without (Tg.KO) the TGFβR.

Results
Despite many CD4 T cells localizing to the granuloma and undergoing T-cell receptor (TCR) activation (pS6), IFNɣ production was not significantly increased in the granuloma compared with a distal lung site (Figure 1). This pattern of localization and activation was found to be similar in the Mtb-specific (but not control) Th1 cells (Figure 2). In contrast, CD4 T cells from TGFβR.KO mice produced more IFNɣ within the granuloma (Figure 3). Lastly, Tg.KO cells transferred into wild-type mice produced increased IFNɣ compared with Tg.WT, mirroring the findings in TGFβR.KO mice (Figure 4).

Conclusion
CD4 T cell production of IFNɣ is decreased within the granuloma, where it can be most effective, despite evidence of ongoing TCR stimulation in Mtb-specific cells. We have shown that by alleviating the effects of TGFβ signaling, even terminally-differentiated Mtb-specific Th1 cells can produce more IFNɣ within the granuloma. While this modest increase suggests that there are additional mechanisms at play which warrant further exploration, these findings have the potential to guide immunotherapeutic development, especially given that TGFβ inhibitors are already in phase III clinical trials for other purposes.

Disclosures
All Authors: No reported Disclosures.
1886. N1,N12-Diacetylspermine as Potential Urinary Biomarker to Monitor Treatment Response and Bacterial Load in Pulmonary Tuberculosis
Authors: Xia Qianjing (Jenny) , Hee Lee Myung , Rhee Kyu , Isa Flonza 
Published: October 2019

Abstract

Background
Adequate control of the global tuberculosis (TB) burden is limited by a lack of accurate measures of treatment efficacy. Current gold standard relies on sputum cultures, which often lag weeks behind time of sample collection. Previous studies have identified urinary N1,N12-diacetylspermine (DiAcSpm) as a potential biomarker of active pulmonary TB (ATB). We aimed to quantify urinary DiAcSpm in participants being treated for ATB and identify its relationship to treatment response.

Methods
Longitudinal urine samples were obtained from two separate cohorts of participants treated for ATB. Cohort one consisted of 34 successfully treated ATB cases with urine collected at weeks 0, 2, 4, 8, 17, 26, and 52. Cohort two consisted of 35 ATB cases under two treatment arms: one arm was successfully treated with the standard therapy of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE), and the other arm received an experimental drug, which was later found to be ineffective against ATB. Urine from cohort two was collected at days 0, 2, 4, and 14. All samples were blinded, randomized, normalized to osmolality and urinary creatinine, and analyzed using high-performance liquid chromatography-mass spectrometry. DiAcSpm concentrations were further tested using ELISA.

Results
Using linear-mixed modeling that adjusted for age, sex, and participant weight, we found that urinary DiAcSpm significantly decreased by week 2 of successful treatment in both cohorts (P < 0.0001). DiAcSpm levels remained unchanged in the ineffective experimental drug group (cohort two), significantly differentiating treatment success and failure by day 14 (P < 0.0001). Additionally, concentrations of urinary DiAcSpm positively correlate with sputum mycobacterial burden (P = 0.0002).These findings were consistent across both methods of detection.

Conclusion
Our results suggest that urinary concentrations of DiAcSpm correlate with TB treatment outcome and mycobacterial disease burden, and have the potential to serve as an early biomarker of TB treatment efficacy.

Disclosures
All Authors: No reported Disclosures.