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Background COVID-19 pandemic caused by SARS-CoV-2 resulted in a global health crisis in 2020. Quarantining, wearing masks and physical distancing- key infection prevention strategies implemented to stop the spread of COVID-19, also led to dramatic decreases in rates of common respiratory viral infection seen in young children. Due to lack of school and daycare exposure, we evaluated a larger than usual number of patients with periodic fevers without any known infectious contacts. Based on this observation, we conducted an analysis of all suspected cases of periodic fevers seen at our institution during the COVID-19 lockdown compared to prior seasons. Methods The clinical charts were queried for all patients presenting to any Lurie Children’s Hospital outpatient specialty clinic or laboratory with ICD diagnosis code of MO4.1 and MO4.8 (all recurrent and periodic fever syndromes) from June 1, 2020 through September 30, 2020, and compared to similar months the previous 2 years (2018 and 2019). Each patient chart was reviewed by the lead investigator to verify all new diagnoses of PFAPA. The number of new patients with PFAPA diagnosis were tallied and analyzed. Statistical comparisons were made using Kruskal-Wallis tests for monthly distributions in different years. Results We noted a significant increase in patients with new PFAPA diagnosis between June through August 2020 compared to similar months in 2018 and 2019 (Figure1). Experienced pediatric infectious disease physicians and rheumatologists diagnosed majority of the cases. During these months, a monthly median (IQR) of 13 (11.5, 14.5) patients were diagnosed among different Lurie specialty clinics, which is more than 2.5 folds increase in new PFAPA patients from the previous two years which were about 5 (3.5, 6) (Figure 2). Number of Patients with New PFAPA Diagnosis There was a significant increase in number of new patients diagnosed with PFAPA between June through August 2020 compared to similar months in 2018 and 2019. Monthly Distribution Summary for New PFAPA Diagnosis Statistical comparisons were made using Kruskal- Wallis tests for monthly distributions in different years Conclusion We observed a significant increase in PFAPA patients referred to our institution soon after introduction of public health measures to slow spread of COVID-19. Given that most children were not in daycare, schools, or camps, we suspect that parents and pediatricians were able to recognize patterns of periodic fevers in children much quicker than preceding years, when fevers would typically be attributed to an infectious process. Disclosures Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial Stipend as Co-editor in Chief, Clinical Therapeutics)Seqirus (Consultant)

Background Immunization prior to transplantation is important due to post-transplant immunosuppression. According to a national study, 15% of pediatric solid organ transplant recipients were hospitalized within 5 years post-transplant for a vaccine preventable illness or RSV. At our large academic pediatric hospital approximately 53% of heart and liver transplant recipients in 2016 -2018 were up to date with tetanus and pneumococcal vaccinations. This QI project was designed to improve our pre-transplant vaccination rates to minimize post-transplant infections. Methods An interdisciplinary team was convened including pharmacists, nurses, nurse practitioners, and physicians from cardiology, hepatology, and infectious diseases. After evaluating our current processes and key drivers, we selected interventions to implement via the PDSA model. Our first intervention was to have team members gain access to our statewide vaccine database (ICARE). Our second cycle was to link ICARE to our electronic medical record system (EPIC) for automatic immunization record integration. Process Map Key Driver Diagram Results Our outcome measure was up to date tetanus and pneumococcal vaccines per the CDC recommendations by age at transplant, as documented in the medical record. We saw an improvement in immunization rates to 100% during the third quarter of 2020 with an overall rate of over 80% for late 2019 - mid 2020. With the understanding that our average wait time for a heart and liver transplant was 2.4 and 3.8 months, respectively, the initiation of our QI project and obtaining access to ICARE by our team members was likely related to the improved vaccination rates. Unfortunately, after the team stopped meeting during the pandemic our immunization completion rates have decreased in 2021, despite implementing institutional access to ICARE. Control Chart Conclusion It is possible to obtain optimal immunization rates for pneumococcal and tetanus vaccines in pediatric heart and liver transplant recipients. Our future interventions include improving vaccinations after catch-up recommendations have been made and sustaining our interventions. Additionally, we look to expand our analysis to include outcomes related to vaccine-preventable diseases after transplantation. Disclosures Jacquie Toia, DNP, RN, APN, QarTek (Board Member) Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial Stipend as Co-editor in Chief, Clinical Therapeutics)Seqirus (Consultant)

Introduction: Hepatitis C virus (HCV) is a major global health issue and successful treatment has been associated with a reduction of risk of all-cause mortality. Advancements have been made in HCV treatment through the use of interferon-free regimens. Most trials have been conducted in HCV genotype (GT) 1 and data for interferon-free regimens in GT4 patients are limited. The aim of this study was to evaluate the safety and efficacy of sofosbuvir plus simeprevir in a real-world cohort of HCV GT4 patients with advanced fibrosis. Patients and Methods: Eighty-seven GT4 treatment-naïve or -Interferon (IFN) ribavirin (RBV) experienced patients treated with sofosbuvir and simeprevir +/- ribavirin (RBV) were enrolled in this cohort study (41% severe fibrosis, 59% cirrhosis). Results: Patients were 51.7% male, 78.2% IFN/RBV treatment-experienced, and 37.9% received RBV treatment. The overall sustained virologic response at least 12 weeks after treatment (SVR12) rate was 87.4% while patients treated with and without RBV had rates of 87.9% and 87% (p = 0.593), respectively, and patients with advanced fibrosis (F3) and patients with cirrhosis had SVR12 rates of 94.4% and 82.4% (p = 0.087), respectively. SVR12 rates in treatment-naïve patients and in IFN/RBV -experienced patients were 78.9% and 89.7% (p = 0.191), respectively. Treatment failure occurred most commonly in patients with cirrhosis and severe disease. The treatment was well tolerated and no patient died or discontinued treatment due to adverse events. Conclusions: Sofosbuvir in combination with simeprevir +/- ribavirin in GT 4 HCV patients with advanced fibrosis achieved high SVR12 rates and was well tolerated. RBV did not appear to increase the rate of SVR12., SCOPUS: ar.j, info:eu-repo/semantics/published

Background The use of multiplex nucleic acid amplification assays to detect respiratory viruses is increasing. However, these tests are expensive, and the clinical significance of a positive result is often unclear. Positive viral results have the potential to decrease antibiotic use and length of stay, but their actual impact is unknown. Methods We completed a retrospective review of all adult patients with positive respiratory viral panel (RVP; GenMark) and/or rapid RSV/influenza PCR tests (Cepheid Xpert) collected within 48 hours of admission to the general inpatient or stepdown units of an academic tertiary care hospital between September 1, 2015 and March 15, 2016. Data collected included demographics, comorbidities, clinical presentation, time of test collection and result, additional diagnostic evaluation, and antibiotic use. Results A total of 221 positive respiratory viral tests were collected on 215 patients during the study period. The median age at time of testing was 56.8 years; 48% were female. Respiratory symptoms were documented in 92.8% of cases. COPD was the most common respiratory co-morbidity (20.2%), while 30% of patients had cancer, and 3.2% were HIV-infected. Respiratory support on admission was common (51.6%). A rapid PCR and RVP were performed in 58.8% of cases, while 28.5% had only an RVP and 12.7% had only a rapid PCR. Of the patients who had a positive rapid PCR, 17.6% also had an RVP done. Antibiotics were started within 24 hours of presentation in 87.4% of all cases and 70.6% of patients who had a positive rapid PCR. Rhinovirus was the most frequently isolated pathogen (44.6% of positive tests) followed by metapneumovirus (14%), respiratory syncytial virus (13.5%), and coronavirus (13.5%). Median time from specimen collection to result was 38.8 hours for RVP, and 15.3% were resulted after patient discharge. For those who had a rapid PCR alone, median time from collection to result was 1.5 hours. Conclusion In this non-critically ill cohort, most patients with positive viral assays received antibiotics, and a substantial number of RVPs were resulted after discharge. This suggests that there are many lost opportunities to impact clinical management with respiratory viral testing. Disclosures M. Miller, GenMark Diagnostics: Grant Investigator, Research support and Salary; R. Jhaveri, GenMark: Investigator, Grant recipient

© 2014 Loizides-Mangold et al. Hepatitis C virus (HCV) infected patients often develop steatosis and the HCV core protein alone can induce this phenomenon. To gain new insights into the pathways leading to steatosis, we performed lipidomic profiling of HCV core protein expressing-Huh-7 cells and also assessed the lipid profile of purified lipid droplets isolated from HCV 3a core expressing cells. Cholesteryl esters, ceramides and glycosylceramides, but not triglycerides, increased specifically in cells expressing the steatogenic HCV 3a core protein. Accordingly, inhibitors of cholesteryl ester biosynthesis such as statins and acyl-CoA cholesterol acyl transferase inhibitors prevented the increase of cholesteryl ester production and the formation of large lipid droplets in HCV core 3a-expressing cells. Furthermore, inhibition of de novo sphingolipid biosynthesis by myriocin - but not of glycosphingolipid biosynthesis by miglustat - affected both lipid droplet size and cholesteryl ester level. The lipid profile of purified lipid droplets, isolated from HCV 3a core-expressing cells, confirmed the particular increase of cholesteryl ester. Thus, both sphingolipid and cholesteryl ester biosynthesis are affected by the steatogenic core protein of HCV genotype 3a. These results may explain the peculiar lipid profile of HCV-infected patients with steatosis.

BackgroundRecently promising trials of innovative biomedical approaches to prevent HIV transmission have been reported. Participants' non-adherence to the prevention methods complicates the analyses and interpretation of trial results. The influence of variable sexual behaviors within and between participants of trials further obscures matters. Current methodological and statistical approaches in HIV-prevention studies, as well as ongoing debates on contradictory trial results, may fail to accurately address these topics.Methodology/Principal FindingsThrough developing a cumulative probability model of infection within HIV prevention trials, we demonstrate how adherence and sexual behavior patterns impact the overall estimate of effectiveness, the effectiveness of prevention methods as a function of adherence, and conclusions about methods' true effectiveness. Applying the model to summary-level data from the CAPRISA trial, we observe markedly different values for the true method effectiveness of the microbicide, and show that if the gel would have been tested among women with slightly different sexual behavior patterns, conclusions might well have been that the gel is not effective.Conclusions/SignificanceRelative risk and adherence analyses in HIV prevention trials overlook the complex interplay between adherence and sexual behavior patterns. Consequently, they may not provide accurate estimates of use- and method-effectiveness. Moreover, trial conclusions are contingent upon the predominant sexual behavior pattern of participants and cannot be directly generalized to other contexts. We recommend researchers to (re)examine their data and use the cumulative probability model to estimate the true method effectiveness, which might contribute to resolving current questions about contradictory trial results. Moreover, we suggest taking into account the issues raised in the design of future trials and in population models estimating the impact of large-scale dissemination of prevention methods. Comprehension of the topics described will help readers to better interpret (apparently contradictory) trial outcomes.