Parainfluenza virus (PIV) may cause life-threatening pneumonia in lung transplant patients and there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, to treat severe PIV type 3 pneumonia in a lung transplant patient. Treatment was well tolerated and associated with improvement in oxygenation and symptoms, along with rapid clearance of PIV. DAS181 should be systematically evaluated for treatment of PIV infection in transplant recipients.

Fructosamine is an alternative method to hemoglobin A1c (HbA1c) for determining average glycemia. However, its use has not been extensively evaluated in persons living with HIV (PLWH). We examined the relationship between HbA1c and fructosamine values, specifically focusing on anemia (which can affect HbA1c) and albumin as a marker of liver disease. We included 345 PLWH from two sites. We examined Spearman rank correlations between fructosamine and HbA1c and performed linear test for trends to compare fructosamine and HbA1c correlations by hemoglobin and albumin quartiles. We examined discrepant individuals with values elevated only on one test. We found a correlation of 0.70 between fructosamine and HbA1c levels. Trend tests for correlations between fructosamine and HbA1c were significant for both albumin (p = 0.05) and hemoglobin (p = 0.01) with the lowest correlations in the lowest hemoglobin quartile. We identified participants with unremarkable HbA1c values but elevated fructosamine values. These discrepant individuals had lower mean hemoglobin levels than those elevated by both tests. We demonstrated a large correlation between HbA1c and fructosamine across a range of hemoglobin and albumin levels. There were discrepant cases particularly among those with lower hemoglobin levels. Future studies are needed to clarify the use of fructosamine for diabetes management in PWLH.

Background: Sickle cell disease (SCD) comprises a group of inherited blood disorders, and is a complex, multi-system, disease. SCD is associated with a variety of clinical complications that affect multiple organ systems. These complications are driven primarily by vaso-occlusion and hemolytic anemia, and can result in end-organ damage and early death. Painful vaso-occlusive crises (VOCs) are a characteristic feature of SCD and can require healthcare intervention. Despite recent advances in the screening, management and treatment of SCD, gaps remain in our understanding of the disease in the real-world setting. These include how best to transition from pediatric to adult care and how to manage specific complications. Currently, most real-world evidence (RWE) is generated from information captured in payer databases, which is not as comprehensive as the information recorded in electronic medical records (EMRs). Despite being potentially valuable sources of real-world, clinical information, EMRs for individual patients in the USA are not centralized, often being held by multiple healthcare providers using different EMRs. This fragmented system prevents generation of clear, comprehensive RWE, both in general and for SCD specifically. Furthermore, there is a lack of harmonization between EMR companies/systems in the types of information included and how it's recorded. A separate approach that collates all available data from EMRs into a single, comprehensive record prior to RWE analysis would therefore greatly improve the accessibility of the available information and the quality of subsequent data analysis. Aims: In contrast to existing RWE, this study explores the value of collating EMRs for each patient into a single, consistently structured format, with the aim of developing richer RWE to complement existing data on SCD. It is hypothesized that the resulting longitudinal overview of each patient's care will contribute to an improved understanding of SCD in the real-world setting: firstly, by better capturing how many VOCs patients with SCD experience, with an indication of the proportion of VOCs that are being home-managed; secondly, by gaining deeper insights into the prevalence and progression of end-organ damage and any association with VOCs; and finally, by highlighting the type and site of care of SCD in the real world (eg medications, treating healthcare professional [HCP] specialties and the type of clinic visited). Study design: The study population will comprise 400 patients with SCD from the USA. Patient recruitment occurs directly via social media and indirectly through a variety of partnerships including HCPs and patient advocacy groups. To enroll, patients sign an informed consent form allowing their de-identified medical information to be shared with third-party organizations to advance SCD research. Enrolled patients gain access to their medical records via a dashboard. The key inclusion criteria are: a confirmed SCD diagnosis (irrespective of phenotype); aged ≥16 years at enrollment; and ≥1 inpatient admission for a VOC in the 12 months prior to enrollment. The key exclusion criterion is the absence of medical records. Components of EMRs collected include doctors' notes, laboratory and test results, clinical imaging and treatment records. Human-curated natural language processing and machine learning is used to extract, structure and code data from the structured sections and unstructured narrative text of the EMR. All medical records, from all visits, will be collected where possible and are expected to comprise ≥7 years of retrospective data for each patient. Results: Between 1 December 2019 and 24 June 2020, a total of 46 patients with a mean age of 36 years (SD 9.7) were enrolled. For each patient, a median of 6.8 years of data from a median of 32.5 providers were obtained. Conclusions: The evidence derived from this study aims to advance the understanding of real-world practices in the management of SCD. It may also provide further learnings regarding the prevalence of complications and any association between VOCs and end-organ damage. Generating a single, structured overview of all EMRs for each patient allows for richer insight generation and a more comprehensive analysis of RWE, compared with existing approaches. The insights gained from this RWE may inform future studies and clinical trials in SCD, with the ultimate aim of improving the quality of life of patients. Disclosures Clay: Novartis: Consultancy; GBT: Consultancy. Bailey:Novartis Pharmaceuticals Corporation: Current Employment. Drozd:F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.; PicnicHealth: Current Employment, Current equity holder in private company. Paulose:Novartis Pharma AG: Current Employment. Ramscar:Novartis Pharma AG: Current Employment. Mace:Roche/Genentech: Ended employment in the past 24 months; PicnicHealth: Current Employment. Wormser:Novartis Pharma AG: Current Employment, Current equity holder in publicly-traded company.

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Background Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease of dysregulated complement activation characterized by hemolysis and thrombosis and is associated with bone marrow failure. PNH can also impair patient quality of life and negatively impact the ability to work. PNH is a rare disease with an estimated incidence of 1 to 1.5 cases per million people globally. Inhibition of complement component 5 (C5) has been shown to reduce intravascular hemolysis, stabilize hemoglobin, reduce the need for blood transfusion, and improve quality of life for patients with PNH. C5 inhibitors eculizumab and ravulizumab are approved in the United States and other countries for treatment of PNH, yet there are limited data on the real-world use of these agents, especially in populations not eligible to participate in registrational clinical trials. Here we describe the COMMODORE Cohort study, which will use a novel patient-centered study design to collect both retrospective and prospective patient data on the real-world use, safety, and effectiveness of eculizumab and ravulizumab, as well as disease burden and outcomes, in patients with PNH in the United States. Study Design and Methods This noninterventional cohort study will collect data using the PicnicHealth digital personal health record platform. This platform uses a novel human-in-the-loop machine learning system to integrate, harmonize, and structure patient data, including clinical notes, medications, laboratory results, and diagnostic reports contained in medical records collected from any healthcare facility in the United States. This study was designed in collaboration with patient advocacy groups to ensure that data generated will answer questions important to the patient community. In contrast to many studies, patients will be directly recruited to participate through multiple avenues, including working with patient advocacy groups and societies as well as outreach through social media and other communication tools. All patients must complete an informed consent form to participate. Patient data is anonymized, and the study complies with the Health Insurance Portability and Accountability Act data security standards. The study will be submitted to IntegReview for institutional review board approval. Patients who report a diagnosis of PNH within the past 5 years and have subsequently been treated with eculizumab or ravulizumab can be included in this study (Figure). Data extracted by the platform will confirm that the patient meets study criteria. The study has 3 arms: arm A is comprised of patients who initiated therapy with eculizumab, arm B is patients who initiated therapy with ravulizumab, and arm C is patients who initiated therapy with eculizumab and later switched to ravulizumab. Exclusion criteria for patients in arms A and B includes treatment with a complement inhibitor prior to PNH diagnosis and treatment with eculizumab or ravulizumab for > 25 weeks. Exclusion criteria for all patients include platelet count < 30,000/μL, absolute neutrophil count < 500/μL, and history of bone marrow transplant. The primary objective is to describe the proportion of patients who do not receive packed red blood cell transfusion. Secondary objectives are to determine the proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and a thromboembolic event and the change in normalized lactate dehydrogenase. Safety objectives are to determine the rates and proportions of selected adverse events. Primary, secondary, and safety objectives will be evaluated from week 5 to 25 of treatment. The effectiveness and safety analyses will be conducted in all patients who fulfill entry criteria and have a minimum of 25 weeks of accrued person-time from treatment initiation. Exploratory analyses assessing long-term experiences and outcomes and will be conducted in all patients who fulfill entry criteria with no minimum treatment duration requirement. Descriptive statistics will be provided. Summary The COMMODORE Cohort study will use a novel, patient-centered approach to data generation including collaborating with patient groups to ensure that the study answers questions important to the PNH community. This approach may serve as a model for future studies evaluating other rare diseases with limited real-world data. Disclosures Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Faghmous:Kite Pharma: Current Employment; F. Hoffmann-La Roche Ltd: Ended employment in the past 24 months, Other: All authors received medical writing support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . Drozd:PicnicHealth: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Katz:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland..