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Glomerular hyperfiltration is common in sickle cell disease (SCD) and precedes proteinuria and declining kidney function. We evaluated hyperfiltration in SCD patients and its "normalization." Routine visit data were collected retrospectively from adult SCD patients in a single centre from 2004 to 2013. Baseline was defined as first available serum creatinine and hyperfiltration as estimated glomerular filtration rates (eGFR) >130 ml/min/1·73 m2 for women and >140 ml/min/1·73 m2 for men. Normalization of hyperfiltration was eGFR reduction to 90-130 ml/min/1·73 m2 for women or 90-140 ml/min/1·73 m2 for men. Among 292 patients, median age was 27 years [interquartile range (IQR):20·0-38·0], and 56·8% had baseline hyperfiltration. Baseline hyperfiltration was inversely associated with age [odds ratio (OR):0·86, 95% confidence interval (CI): 0·82-0·90; P < 0·0001], male sex (OR:0·16, 95% CI: 0·07-0·41; P = 0·0001), haemoglobin (OR:0·76, 95% CI 0·61-0·94; P = 0·01), weight (OR:0·96, 95% CI: 0·93-0·99; P = 0·004), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use (OR:0·08, 95% CI: 0·01-0·75; P = 0·03), and positively with hydroxycarbamide use (OR:2·99, 95% CI: 1·18-7·56; P = 0·02). Of 89 hyperfiltration patients without baseline proteinuria, 10 (11·2%) developed new-onset proteinuria [median 1·05 years (IQR:0·63-2·09)]. Normalization of hyperfiltration was less likely with higher baseline eGFR [hazard ratio (HR):0·90, 95% CI: 0·86-0·95; P < 0·0001] and more likely in males (HR:6·35, 95% CI:2·71-14·86

BACKGROUND: Severe acute malnutrition (SAM) is common in low-income countries such as Malawi and is associated with high mortality in young children. OBJECTIVE: To improve recognition and management of SAM in a tertiary hospital in Malawi. METHODS: The impact of multifaceted quality improvement interventions in multiple process measures pertaining to identification and management of children with SAM using a before-after design was assessed. Interventions included focused training for clinical staff, reporting process measures to clinical staff, and mobile phone-based group messaging for enhanced communication. This initiative focused on children aged 6–36 months admitted to Kamuzu Central Hospital in Malawi from 18 September 2019 to 17 March 2020. Before-after comparisons were made with baseline data from the year prior, and process measures within this intervention period that included three plan-do-study-act (PDSA) cycles were compared. RESULTS: During the intervention period, 418 children had SAM and in-hospital mortality was 10.8%, which was not significantly different than the baseline period. Compared with the baseline period, there was significant improvement in the documentation of full anthropometrics on admission, blood glucose test within 24 hours of admission and HIV testing results by discharge. During the intervention period, amidst increasing patient census with each PDSA cycle, three process measures were maintained (documentation of full anthropometrics, determination of nutrition status and HIV testing results) and there was significant improvement in blood glucose documentation. CONCLUSIONS: Significant improvement in key quality measures represents early progress towards the larger goal of improving patient outcome, most notably mortality, in children admitted with SAM.

Pediatric acute respiratory illness (ARI) is one of the most common reasons for evaluation at peripheral health centers in sub-Saharan Africa and is frequently managed based on clinical syndrome alone. Although most ARI episodes are likely caused by self-limited viral infections, the majority are treated with antibiotics. This overuse contributes to the development of antimicrobial resistance. To evaluate the preliminary feasibility and potential impact of adding pathogen-specific and clinical biomarker diagnostic testing to existing clinical management algorithms, we conducted a prospective, observational cohort study of 225 children presenting with malaria-negative, febrile ARI to the outpatient department of a semi-urban peripheral health facility in southwestern Uganda from October 2019 to January 2020. In addition to routine clinical evaluation, we performed influenza and Streptococcus pneumoniae antigen testing and measured levels of C-reactive protein, procalcitonin, and lactate in the clinic’s laboratory, and conducted a follow-up assessment by phone 7 days later. Almost one-fifth of participants (40/225) tested positive for influenza. Clinical biomarker measurements were low with C-reactive protein of >40 mg/L in only 11% (13/222) of participants and procalcitonin >0.25 ng/mL in only 13% (16/125). All but two children received antibiotic treatment; only 3% (7/225) were admitted. At follow-up, 59% (118/201) of caregivers reported at least one persistent symptom, but fever had resolved for all children. Positive influenza testing was associated with persistent symptoms. In summary, we demonstrate that simple, rapid pathogen-specific testing and biomarker measurement are possible in resource-limited settings and could improve syndromic management and, in turn, antibiotic stewardship. IMPORTANCE Globally, respiratory illness is one of the most common reasons that children seek care. It is often treated inappropriately with antibiotics, which can drive the development of antibiotic resistance. In resource-rich settings, testing for specific pathogens or measurement of clinical biomarkers, such as procalcitonin and C-reactive protein, is often employed to help determine which children should receive antibiotics. However, there are limited data on the use of these tests in resource-constrained, outpatient contexts in sub-Saharan Africa. We enrolled children with respiratory illness presenting to a clinic in southwestern Uganda and performed testing for influenza, Streptococcus pneumoniae, C-reactive protein, and procalcitonin on-site. Almost all children received antibiotics. We demonstrate that employing clinical algorithms that include influenza and clinical biomarker testing could significantly decrease antibiotic prescriptions. Our study therefore provides preliminary data to support the feasibility and potential utility of diagnostics to improve management of respiratory illness in resource-constrained settings.

We evaluated the prevalence of rapid decline in kidney function, its potential risk factors and influence upon mortality in sickle cell disease (SCD) in a retrospective single-center study. Rapid decline of kidney function was defined as estimated glomerular filtration rate (eGFR) loss of >3.0 ml/min/1.73 m(2) per year. A multivariable logistic regression model for rapid eGFR decline was constructed after evaluating individual covariates. We constructed multivariate Cox-regression models for rapid eGFR decline and mortality. Among 331 SCD patients (median age 29 years [intergquartile range, IQR: 20, 41]; 187 [56.5%] female) followed for median 4.01 years (IQR: 1.66, 7.19), rapid eGFR decline was noted in 103 (31.1%). History of stroke (odds ratio [OR]: 2.91, 95% confidenc interval [CI]: 1.25 – 6.77) and use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (OR: 3.17, 95%CI: 1.28–7.84) were associated with rapid eGFR decline. The rate of eGFR change over time was associated with mortality (hazard ratio [HR]: 0.99, 95%CI: 0.984-0.995, p = 0.0002). In Cox-regression, rapid eGFR decline associated with mortality (HR: 2.07, 95%CI: 1.039-4.138, p = 0.04) adjusting for age, sex and history of stroke. Rapid eGFR decline is common in SCD and associated with increased mortality. Long-term studies are needed to determine whether attenuating loss of kidney function may decrease mortality in SCD.

BACKGROUND: In children in sub-Saharan Africa, severe anaemia (SA) is an important cause of mortality and malaria is a primary cause. The World Health Organization (WHO) recommends blood transfusion for all children with haemoglobin (Hb)

Background Health care personnel (HCP) are at high risk for exposure to the SARS-CoV-2 virus. While personal protective equipment (PPE) may mitigate this risk, prospective data collection on its use and other risk factors for seroconversion in this population is needed. Objective The primary objectives of this study are to (1) determine the incidence of, and risk factors for, SARS-CoV-2 infection among HCP at a tertiary care medical center and (2) actively monitor PPE use, interactions between study participants via electronic sensors, secondary cases in households, and participant mental health and well-being. Methods To achieve these objectives, we designed a prospective, observational study of SARS-CoV-2 infection among HCP and their household contacts at an academic tertiary care medical center in North Carolina, USA. Enrolled HCP completed frequent surveys on symptoms and work activities and provided serum and nasal samples for SARS-CoV-2 testing every 2 weeks. Additionally, interactions between participants and their movement within the clinical environment were captured with a smartphone app and Bluetooth sensors. Finally, a subset of participants’ households was randomly selected every 2 weeks for further investigation, and enrolled households provided serum and nasal samples via at-home collection kits. Results As of December 31, 2020, 211 HCP and 53 household participants have been enrolled. Recruitment and follow-up are ongoing and expected to continue through September 2021. Conclusions Much remains to be learned regarding the risk of SARS-CoV-2 infection among HCP and their household contacts. Through the use of a multifaceted prospective study design and a well-characterized cohort, we will collect critical information regarding SARS-CoV-2 transmission risks in the health care setting and its linkage to the community. International Registered Report Identifier (IRRID) DERR1-10.2196/25410

The effect of SARS-CoV-2 infection on response to mRNA-based SARS-CoV-2 vaccines is not well-described. We assessed longitudinal SARS-CoV-2-specific antibody responses pre- and post-vaccination among individuals with and without prior infection. The antibody response to the first vaccine dose was almost two-fold higher in individuals who were seropositive before vaccination compared to those who were seronegative, suggesting that prior infection primes the immune response to the first dose of mRNA-based vaccine.

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics.

Severe acute malnutrition (SAM) is a major cause of childhood mortality in resource-limited settings. The relationship between clinical factors and adherence to the 'WHO 10 Steps' and mortality in children with SAM is not fully understood.Data from an ongoing prospective observational cohort study assessing admission characteristics, management patterns and clinical outcome in children aged 6-36 months admitted to a tertiary hospital in Malawi from September 2018 to September 2019 were analysed. Data clerks independently collected data from patients' charts. Demographics, clinical and nutritional status, identification of SAM and adherence to the 'WHO 10 Steps' were summarised. Their relationship to in-hospital mortality was assessed using multivariable logistic regression.Of the 6752 patients admitted, 9.7% had SAM. Mortality was significantly higher in those with SAM (10.1%HIV infection remains an important predictor of mortality in children with SAM. IV fluids should be avoided in those without shock. Early identification of SAM by the clinical team represents a focus of future quality improvement interventions at this facility.

As the field of global child health increasingly focuses on inpatient and emergency care, there is broad recognition of the need for comprehensive, accurate data to guide decision-making at both patient and system levels. Limited financial and human resources present barriers to reliable and detailed clinical documentation at hospitals in low-and-middle-income countries (LMICs). Kamuzu Central Hospital (KCH) is a tertiary referral hospital in Malawi where the paediatric ward admits up to 3000 children per month. To improve availability of robust inpatient data, we collaboratively designed an acute care database on behalf of PACHIMAKE, a consortium of Malawi and US-based institutions formed to improve paediatric care at KCH. We assessed the existing health information systems at KCH, reviewed quality care metrics, engaged clinical providers and interviewed local stakeholders who would directly use the database or be involved in its collection. Based on the information gathered, we developed electronic forms collecting data at admission, follow-up and discharge for children admitted to the KCH paediatric wards. The forms record demographic information, basic medical history, clinical condition and pre-referral management; track diagnostic processes, including laboratory studies, imaging modalities and consults; and document the final diagnoses and disposition obtained from clinical files and corroborated through review of existing admission and death registries. Our experience with the creation of this database underscores the importance of fully assessing existing health information systems and involving all stakeholders early in the planning process to ensure meaningful and sustainable implementation.

Although renin-angiotensin-aldosterone system (RAAS) blocking agents decrease albuminuria in short-term studies, there is no evidence confirming their long-term efficacy in sickle cell disease (SCD). In a single-centre, retrospective study, we evaluated the long-term effect of RAAS blocking agents on proteinuria and declining estimated glomerular filtration rates (eGFR). Eighty-six patients on RAAS blocking agents for proteinuria, followed for a median of 2.28 years, were compared with 68 patients with proteinuria followed for 2.24 years who were not receiving such treatment. The log odds of proteinuria decreased over time in patients on RAAS blocking agents (β: −0.23, p = 0.03) and in the non-treatment group (β: −0.54, p < 0.0001), but was not statistically different between both groups (β: 0.31, p = 0.063). The eGFR declined over time in patients on RAAS blocking agents (β: −2.78, p < 0.0001) and in those not on such treatment (β: −4.7, p < 0.0001), and was statistically different between both groups (β: 1.9, p = 0.0002). Baseline eGFR was associated with mortality (Hazard rato: 0.97, p < 0.0001), but RAAS blocking agents had no significant effect on mortality. These data suggest that RAAS blockade may slow the loss of kidney function in SCD.

Introduction Individuals with sickle cell disease (SCD) in resource-rich countries are now living longer due to the implementation of newborn screening, use of prophylactic penicillin, and introduction of hydroxyurea. The impact of SCD on the bone marrow and peripheral blood counts as individuals with SCD age is not well described in the hydroxyurea era. As a result of increased red blood cell (RBC) turnover due to hemolysis in SCD, potential ineffective erythropoiesis, and well-described systemic inflammatory processes, the increased stress in the bone marrow may manifest as decreased peripheral blood cell counts over time in a during an aging process unique to those with SCD. Objective The objective was to model routine clinical blood measurements (n=5,328) with a longitudinal cohort of 447 patients, resulting in models of circulating blood counts as a potential marker of bone marrow function across the lifespan in adults with SCD. Our working hypothesis was that increasing age would be associated with decreases in certain blood counts, with trends modified by SCD genotype severity. Methods In this large, single institution retrospective cohort study, we analyzed blood count measurements from adults with SCD. We used an accelerated longitudinal cohort design to examine changes in white blood cell count (WBC), hemoglobin (HGB), absolute reticulocyte count (ARC), and platelet count over time. Genotypes were grouped as severe (HbSS or HbSβ 0-thalassemia; n=301), non-severe (HbSC or HbSβ +-thalassemia; n=136), or other (n=10). For HGB and ARC, we adjusted for estimated glomerular filtration rate (eGFR) and serum creatinine. Results Patients ranged in age at enrollment from 18 to 84 (M = 31.9, SD=12.9), with median follow-up time of 3.6 years and a median of 6 measurements per patient. Overall, HGB and ARC decreased across the lifespan; however, trends were moderated by genotype. Compared to individuals with non-severe genotypes, those with the severe genotypes had consistently lower HGB levels that did not differ by age. For ARC, the severe genotypes had higher levels in young adulthood, which slowly decreased with age. WBC also decreased with age for this group. In contrast, individuals with the non-severe genotype showed an increase in WBC by age. Platelet counts decreased with increasing age for those with the severe genotype while those with non-severe genotypes showed an increase with age. Conclusion Severe SCD genotypes are associated with decreases in HGB, ARC, WBC, and platelet count by age. For HGB and ARC, these declines are significantly attenuated by renal function, suggesting that such declines are largely related to worsening renal function with age. However, an intrinsic bone marrow contribution to this aging process should also be explored in future studies. Decreases in WBC and platelet count with time, observed in the severe genotypes, support the presence of pathological processes of bone marrow dysfunction that may worsen with age. A possible etiology of the increasing bone marrow dysfunction in SCD may be a result of bone marrow exhaustion or cellular senescence. Prospective studies to explore contributors to reduced blood counts during the aging process in individuals with SCD are needed. We are actively exploring potential biomarkers associated with this process. Figure 1 Figure 1. Disclosures Carden: Forma Therapeutics: Current Employment. Derebail: Novartis: Consultancy; UpToDate: Patents & Royalties; Travere Therapeutics: Consultancy; Bayer: Consultancy. Ataga: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Background Patients receiving outpatient parenteral antimicrobial therapy (OPAT) experience high rates of unplanned readmissions. To inform interventions that may reduce risk of unplanned readmissions during OPAT, we examined the frequency and reasons for readmission in a large cohort of OPAT patients. Methods We analyzed data on all patients enrolled in UNC’s OPAT program from February 2015-February 2020. Patients were evaluated by an infectious diseases (ID) physician prior to OPAT enrollment, discharged with >14 remaining days of prescribed therapy, and received care coordination and systematic monitoring by an ID pharmacist. We abstracted EHR data into a REDCap database to ascertain information on each patient’s OPAT course and readmission details: length of stay, primary ICD-9-CM/ICD-10-CM diagnosis code associated with readmission, and reason for readmission from clinical notes. Diagnosis codes and notes were adjudicated and summarized by a multidisciplinary team. Results Among 1,165 OPAT courses, 19% resulted in at least one readmission during therapy, lasting for a median length of stay of 5 days. Among those patients who were readmitted during OPAT, the median time from OPAT start to readmission was 17 days (interquartile range, IQR: 8-29 days). 66% of readmissions preceded the scheduled follow-up appointment during OPAT (median time to scheduled follow-up was 27 days, IQR: 15-35 days). 55% of readmissions were unrelated to OPAT diagnosis. Based on ICD-9-CM/ICD-10-CM code classifications, the most common infectious diseases-related reasons for readmission were worsening OPAT infection (18%), OPAT-related adverse drug reaction (12%), and new infection (11%). Conclusion One-fifth of OPAT courses resulted in readmission during therapy. Half of readmissions were associated with OPAT or other infection, and half were for other reasons. Earlier post-discharge follow-up by a multidisciplinary team (including primary care providers, case management, and OPAT) might prevent infection-related readmissions for OPAT patients. Future work should also address the need for enhanced care coordination with non-infectious disease providers to manage OPAT patients. Disclosures All Authors: No reported disclosures

Background At hospital discharge, patients enter a transition period that carries risks for their health and access to care, particularly those receiving home infusion. In April 2019, to enhance care coordination at discharge, our OPAT program implemented a structured telephone outreach program. Methods Starting in April 2019, the UNC OPAT program rolled out a patient outreach intervention. Within approximately 3 days after discharge, a pharmacist or nurse coordinator called the patient or caregiver to discuss UNC’s OPAT program, review all medications and potential adverse effects, discuss home infusion and line care, schedule relevant follow-up appointments and transportation, and address patient/caregiver concerns. To evaluate dissemination and impact, we analyzed data from UNC OPAT patients from April 2019-May 2020. We abstracted EHR data for unplanned readmissions and adverse events (hepatotoxicity, nephrotoxicity, neutropenia, eosinophilia, thrombocytopenia, creatine kinase elevation, rash, Clostridioides difficile infection, line complications). We estimated risk differences (RD) to compare outcomes between contacted versus uncontacted patients. To provide context, we also assessed unplanned readmissions and adverse events in a historical control period from April 2018-March 2019, before implementation of the outreach program. Results After rollout of the outreach program, 374 patients completed their OPAT course and all were targeted for outreach. The success rate of contacting patients was 61%. Median age was similar between contacted and uncontacted patients (52 versus 55). Unplanned readmissions occurred less frequently for contacted patients (14% versus 21%; RD -7%; 95%CI -15%, 1%). Risk of adverse events was similar between contact groups (58% versus 54%; RD 4%; 95%CI -6%, 15%). In the historical control period (n=287, median age 56), unplanned readmission risk was 22% and adverse event risk was 63%. Conclusion Patients who completed the outreach phone call had lower risk of readmission compared to those who could not be reached. This intervention may be a simple, low-cost way to reduce readmissions for OPAT patients, but further study and a sustainable reimbursement structure are needed. Disclosures All Authors: No reported disclosures

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have sepsis of bacterial causes. The protocol includes a detailed clinical assessment with vital sign measurements, strict aseptic blood culture protocol with state-of-the-art microbial analyses and RNA-sequencing and metagenomics evaluations of host responses and pathogens, respectively. We also discuss the directions of a brief analysis plan for RNA sequencing data. This study will provide robust epidemiological data for sepsis in neonates and young infants in a setting where sepsis confers an inordinate burden of disease.

Background In 2020, COVID-19 spurred unprecedented change in the delivery of routine clinical care. The UNC OPAT program staff, previously accustomed to in-person collaboration in the hospital, became geographically distant amid North Carolina’s partial shutdown starting in March 2020. Team members relied on teleworking and many OPAT clinic visits shifted to phone and video telehealth. We assessed how COVID-19 impacted our care of OPAT patients including follow-up visits and readmissions. Methods UNC’s OPAT database contains clinical and demographic information on all patients on OPAT for at least 14 days who received specialized monitoring program led by an infectious diseases (ID) pharmacist, after evaluation by an ID physician. For all OPAT courses that ended between 3/1/20 and 5/20/20 (last available data cut), we assessed the length of OPAT treatment course, readmissions, adverse events, follow-up ID clinic visits, and the method of follow up visit utilized. We compared these measurements to historical baseline data from 3/1/19 to 5/20/19. Results During the 2020 period, 73 patients completed OPAT, with median OPAT enrollment lasting 36 days, which was similar to 2019 data (70 patients; median OPAT enrollment of 35 days). During the 2019 period, 93% of patients attended a follow up visit with an infectious diseases clinician, all of which took place in person. During the 2020 (COVID-19) period, 85% of patients attended an ID follow up visit; contrary to 2019, 42% of these visits took place in person, 45% were by phone and 13% were via a telemedicine video service. Readmission rates were similar across the two time periods (16% during COVID-19 vs 14% during 2019 comparison time period, P=0.72). Conclusion UNC OPAT continued through the emergence of COVID-19 as an essential service for a high patient volume by adapting its care delivery and follow-up visit protocols to include virtual care options. Readmission rates for OPAT patients during COVID-19 were comparable to historical baseline data. Disclosures All Authors: No reported disclosures

RATIONALE AND OBJECTIVE: Progression of chronic kidney disease (CKD) in sickle cell disease (SCD) and its risk factors remain poorly defined. We identified characteristics associated with CKD as well as decline of estimated glomerular filtration rate (eGFR) and presence of proteinuria over time in adults with SCD. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: SCD patients ≥ 18 years old in a single center from 2004–2013. PREDICTORS: Baseline clinical and laboratory measures, comorbidities, SCD-related complications and severity of genotypes defined as severe (HbSS/HbSβ(0) thalassemia) or mild (HbSC/HbSβ(+) thalassemia). OUTCOMES: Presence at baseline of CKD, defined as eGFR < 90 mL/min/1.73 m(2) or proteinuria as ≥1+ greater on urinalysis or current kidney transplant or dialysis; change in eGFR; and incident proteinuria. ANALYTICAL APPROACH: Logistic regression for baseline CKD. Linear mixed effects model for eGFR decline and generalized linear mixed effects model for proteinuria during the study period evaluating for interaction with time. Stratified by genotype severity. RESULTS: Among 427 patients, 331 had ≥ 2 measures of creatinine. Over median follow-up of 4.01 (interquartile range, 1.66–7.19) years, the annual eGFR decline was 2.05 mL/min/1.73 m(2) for severe genotypes (p

Background The use of multiplex respiratory viral panels (RVP) is increasing. They have the potential to reduce unnecessary antibiotic use, but data are limited on their clinical effectiveness. Our objective was to estimate risk differences for antimicrobial de-escalation (discontinuation, intravenous to oral, or spectrum narrowing) between different sequences and results of RVP and rapid polymerase chain reaction (PCR) tests for influenza +/− respiratory syncytial virus. Methods We conducted a retrospective chart review of adults (age ≥18 years) admitted to a floor or stepdown unit at University of North Carolina Hospitals who had a respiratory viral test (RVT) within 48 hours of admission between September 2015 and April 2016. We estimated 3-day RDs for the relation between RVT and antimicrobial de-escalation. To control confounding and account for the 37-hour mean lag between PCR (faster) and RVP (slower) tests resulting, we leveraged the treatment decision design over a series of 1:1 matched cohort studies. Each targeted a clinically relevant scenario: (1) ordering RVP test (vs no RVP order) after learning PCR status; (2) learning RVP+ result (vs. no RVP result) after knowing PCR status; (3) learning RVP+ result (vs. RVP–) after knowing PCR–status; and (4) learning RVP+ result (vs. RVP–) given no prior PCR. For each subcohort, referent patients were matched to index patients by race, gender, RVT in prior month (y/n), age (±10 years), and season (±1.7 months). Results The overall cohort (n = 1,342) was 61% White, 29% African American, and 51% female. Median age was 56 years (IQR 39–69). Across all matched subcohorts (Figure 1), the matching success rate was 79–88% and referent frequency of antimicrobial de-escalation ranged 0.6%–1.9%. In scenario 1, ordering RVP results was associated with higher de-escalation (3-day RD 7.6%; 95% confidence intervals [CI] 3.2%, 12.1%). In scenarios 2–4, learning RVP+ results was associated with more frequent de-escalation (3-day RDs 14.8%, 13.8%, and 15.4%). Conclusion RVP testing and positive RVP results were associated with increased antimicrobial de-escalation, although de-escalation was overall infrequent. Future research should assess effect modification across subgroups and evaluate cost-effectiveness. Disclosures All authors: No reported disclosures.

Introduction:Chronic kidney disease (CKD) is common in sickle cell disease (SCD). We have recently reported on the progression of CKD in SCD and factors associated with it (Ciccone EJ et al, ASH, 2016). The purpose of this study was to evaluate the prevalence of rapid decline in kidney function, factors associated with such decline, and the association of rapid decline in kidney function with mortality in adult patients with SCD. Methods: We conducted a retrospective study of patients seen between July 2004 and December 2013 at an adult Sickle Cell Clinic. Patients had confirmed diagnoses of SCD, were at least 18 years old, and were in non-crisis state. We excluded patients with histories of HIV, hepatitis B and C, or systemic lupus erythematosus. Clinical and laboratory variables were obtained from medical records. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Rapid decline of kidney function was defined as eGFR loss of >3.0 ml/min/1.73 m2per year during the observation period. Logistic regression was used to model the association of rapid eGFR decline with clinical and laboratory variables, adjusting for age and sex. Multivariable analysis with variable selection was performed with backward elimination from the following initial variables - hemoglobin, reticulocyte count, lactate dehydrogenase, baseline eGFR, history of stroke, hydroxyurea therapy, systolic blood pressure, use of ACE inhibitors/angiotensin receptor blockers (ACE-I/ARB) and history of diabetes. Since proteinuria measures were missing for many patients, we performed sensitivity analyses with 1) exclusion of proteinuria, 2) inclusion of only patients with available values, 3) assignment of no proteinuria to those missing values, or 4) assignment of proteinuria to those missing values. Age- and sex- adjusted Cox proportional hazards models were used to evaluate the association of the slope of eGFR (continuous variable) or rapid decline in eGFR (binary variable) with mortality. The slope of eGFR was estimated by linear regression modeling of eGFR over time. Kaplan-Meier estimates of survival probabilities for rapid and non-rapid decline groups were obtained, and the log-rank test was used to compare the survival probabilities for the two groups. Results: Three hundred and thirty-one SCD patients with at least two eGFR measurements(SS = 218, SC = 67, Sβ0= 18, Sβ+= 22, SE = 2, SD = 2, SHPFH = 2), median age of 29 years (IQR: 20 - 41 years) were evaluated and followed for a median of 4.01 years (IQR: 1.66, 7.19). Rapid decline of eGFR (>3.0 ml/min/1.73 m2per year) was noted in 103 (31.1%) patients; 80 (33.9%) with severe genotype (HbSS/HbSβ0thalassemia) and 21 (23.6%) with mild genotype (HbSC/HbSβ+thalassemia).Baseline laboratory factors significantly associated with rapid decline in eGFR were hemoglobin (p = 0.007), ferritin (p = 0.01), and baseline eGFR (p = 0.01) (Table 1). There was a trend towards an association (p = 0.06) with baseline proteinuria (at least 1+ on dipstick urinalysis). Clinical variables significantly associated with eGFR decline were history of stroke (p = 0.002) and use of ACE-I/ARB (p = 0.006). In multivariable analysis, history of stroke (estimate: 1.07, p = 0.01) and use of ACE-I/ARB (estimate: 1.15, p = 0.01) were associated with rapid eGFR decline when proteinuria was excluded from the model or proteinuria status was assigned to those with missing values. When we limited the dataset to those with available values for proteinuria, only history of stroke (estimate: 2.00, p = 0.007) was associated with rapid decline in eGFR. Finally, we observed an association of the slope of eGFR change over time with mortality (hazard ratio [HR]: 0.99, p = 0.0002). Rapid decline in eGFR was significantly associated with increased mortality compared with eGFR decline of ≤ 3 ml/min/1.73 m2per year (HR: 2.40, p = 0.005). Kaplan-Meier estimates also showed significantly lower survival probabilities for patients with rapid eGFR decline (log-rank test; p = 0.0002) (Figure 1). Conclusion:Rapid decline in eGFR is common in SCD. Use of ACE-I/ARB and history of stroke are associated with rapid decline in renal function. Rapid decline in eGFR is associated with an increased risk of death in SCD. Long-term studies are required to determine if therapies that may reduce loss of kidney function may decrease mortality in SCD. Disclosures Ataga: Pfizer: Research Funding; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria; Modus Therapeutics: Honoraria; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Background Multiplex nucleic acid amplification assays (NAATs) are increasingly used to evaluate respiratory illnesses. Viral diagnosis has the potential to change clinical management and, specifically, decrease antibiotic use. However, the assays are expensive, and their effect on clinical management is unknown. This study evaluated the incremental impact of a multiplex respiratory viral panel after negative rapid influenza testing. Methods We completed a retrospective review of all adult patients with respiratory viral panel (RVP; GenMark) and/or rapid influenza or RSV/influenza PCR tests (PCR; Cepheid Xpert) collected within 48 hours of admission to non-ICU, inpatient units from September 1, 2015 to April 15, 2016. We matched hospitalizations with a positive RVP simultaneously with or following negative PCR testing (PCR−RVP+) 1:1 with patient encounters with negative rapid PCR testing only (PCR−). Matching of the referent PCR-group occurred without replacement based on age (±10 years), sex, race, season of testing (±50 days), and any respiratory viral test in the prior 30 days. The primary outcome was a change in management, defined as antimicrobial de-escalation (discontinuation, switch from intravenous to oral administration, and/or narrowing of spectrum), antiviral initiation, and/or change in isolation precautions. Results During the study period, there were 153 PCR−RVP+ patient encounters and 524 with PCR− testing only from which we identified 134 matched pairs. In the matched cohort, the median age was 60 years (IQR: 41–71), 47.8% were female, and 34.3% were non-White. Respiratory viral testing was associated with management change in 3.7% of PCR− and 23.9% of PCR−RVP+ patients (risk difference 20.1%; 95% CI 12.2–28.0%). Antimicrobial de-escalation did not occur after testing for any PCR- patients but did occur for 15.7% of PCR−RVP+ patients (95% CI 9.5–21.8%). Conclusion Among patients with negative rapid influenza testing, a subsequent or simultaneous positive RVP was associated with a higher frequency of antibiotic de-escalation. This suggests multiplex NAATs could play a role in improving antimicrobial stewardship in the setting of respiratory illness. Disclosures M. Miller, GenMark: Investigator, Research support. R. Jhaveri, GenMark: Investigator, Research support.

Introduction: Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD). Despite current practice and recent NHLBI guidelines, which recommend screening and treatment for albuminuria, the progression of CKD in SCD and factors associated with such progression remain poorly defined. The purpose of this study was to evaluate the prevalence of CKD and its rate of progression in adult SCD patients. We also evaluated the laboratory and clinical factors associated with CKD progression. Methods: We conducted a retrospective study of patients seen between July 2004 and December 2013 at an adult Sickle Cell Clinic. Patients had confirmed diagnoses of SCD, were at least 18 years old, and were in the non-crisis state at the time of evaluation. Patients were excluded for histories of HIV, hepatitis B and C, and systemic lupuserythematosus. Clinical and laboratory variables were obtained from medical records. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation.Presence of CKD was assessed by using a modification of the Kidney Disease Improving Global Outcomes clinical practice guidelines that incorporateseGFR and levels of albuminuria. CKD was defined aseGFR Results: Four hundred and twenty six patients with SCD (SS = 268, SC = 98, Sb0 = 22, Sb+ = 29, SE = 3, SD = 2, SHPFH = 4), median age of 29.5 years (IQR: 20 - 41 years), were evaluated. CKD at baseline was observed in 92 patients (21.6 %). The rate of decline in eGFR over time was 2.1 mL/min per 1.73 m2 per year (SE: 0.11, p < 0.0001) (Figure 1). Baseline laboratory factors that were significantly associated with decline ineGFR inunivariate analyses were hemoglobin, lactate dehydrogenase, indirect bilirubin, ferritin, hematuria, urine specific gravity, and proteinuria (at least 1+ on dipstick urinalysis). Clinical variables significantly associated witheGFR decline inunivariate analyses were weight, history of acute chest syndrome,history of stroke, chronic transfusion, systolic blood pressure, diastolic blood pressure, and use of ACE inhibitors/angiotensin receptor blockers (ACE-I/ARB). Multivariable analyses showed that the rate ofeGFR decline was dependent on the status of having proteinuria (estimate: -3.96, p < 0.0001), age (estimate: -0.05, p Conclusion: eGFR declined at a rate of 2.1 mL/min per 1.73 m2 per year in adult patients with SCD. Proteinuria, age, acute chest syndrome, stroke, and higher systolic blood pressure were associated with an increased rate of decline in eGFR. However, heavier weight and chronic red cell transfusions were associated with less severe eGFR decline. Better understanding of these relationships and their pathophysiology is needed so that we can modify identified risk factors and attenuate the loss of kidney function in SCD. Disclosures No relevant conflicts of interest to declare.

Background The pathogenesis of immunodeficiency due to human immunodeficiency virus (HIV)-1 is incompletely understood, but immune activation is believed to play a central role. Immunomodulatory agents that decrease immune activation may be useful in the treatment of HIV-1 infection. Methodology A randomized, double blind, placebo-controlled pilot study of leflunomide for 28 days was performed in participants with HIV-1 infection who were not receiving antiretroviral therapy. Participants randomized to leflunomide were subsequently treated with cholestyramine until leflunomide levels were below detection limit. Findings Treatment with leflunomide was well tolerated with mostly low-grade adverse events. Leflunomide administration reduced cycling of CD4 T cells (by ex vivo bromodeoxyuridine uptake and Ki67 expression) and decreased expression of activation markers (HLA-DR/CD38 co-expression) on CD8 T cells in peripheral blood. In addition, decreased expression of HIV-1 co-receptors was observed in both CD4 and CD8 T cells in the leflunomide group. There were no significant changes in naïve and memory T cell subsets, apoptosis of T cells or markers of microbial translocation. Conclusions Leflunomide was effective in reducing immune activation in the setting of chronic HIV-1 infection suggesting that targeting immune activation with immunomodulatory agents may be a feasible strategy. Trial Registration ClinicalTrials.gov NCT00101374