P094 Comprehensive comparison of juvenile-onset systemic lupus erythematosus guidelines for diagnosis and management to those used in adult-onset disease

Abstract Background/Aims Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune disorder that causes multisystem damage. Paucity of data limits the evidence upon which to base recommendations for diagnosis, monitoring, and management of JSLE. JSLE patients often present more acutely, with more severe complications and greater need for corticosteroids and disease-modifying therapies earlier in life when compared to those with adult-onset SLE (aSLE). The SHARE initiative generated a set of guidelines to standardise JSLE care across Europe. This aim was to undertake a comprehensive comparison aimed at comparing the SHARE guidelines to those developed by the BSR (for aSLE) to identify similarities, differences, and areas in which more research was needed. Methods The SHARE evidence-based, consensus-derived recommendations were established by a European wide panel of paediatric rheumatologists according to EULAR standard operating procedures using a systematic literature search with strict inclusion criteria. Adult-derived evidence was included when lack of paediatric literature existed but reviewed to adapt adult guidelines to be more suitable for paediatric use. The BSR guidelines built upon existing EULAR guidelines, selecting specific recommendations by prioritisation. Both SHARE and BSR used the same method of validating guidelines using Level of Evidence, grade of recommendation and strength of agreement by the panel (SOA) to support their recommendations. A systematic comparison was performed by identifying specific subgroups of recommendations related to: diagnosis, background, neuropsychiatric and monitoring and management guidelines. These subgroups were then compared by assessing the number of guidelines related to each group and the average SOA for each. A detailed comparison into the specific guidelines was then performed to provide in depth analysis of the similarities and differences between the groups and identify areas missing and where more work was needed. Results There are many similarities between the two sets of recommendations. Although some of these are a result of the manifestations being the same in adults and children, a significant proportion of these similarities were due to the lack of background data to base recommendations on for JSLE. Therefore, adult-derived guidelines, particularly the EULAR guidelines have been used which were also used as background for BSR recommendations. A key difference was the lack of recommendations regarding neuropsychiatric manifestations (NP-aSLE) in adult-onset disease. A detailed comparison between individual guidelines has been generated and potential reasons for the discrepancies between the guidelines identified. Conclusion The results demonstrate the need for significantly more research to inform generation of more specific JSLE guidelines, particularly in management of the disease manifestations specific to children. Many similarities between these adult and paediatric guidelines underline the importance of generating common guidelines where possible for JSLE and aSLE. More work is needed in NP-aSLE to produce more balanced generalised results. Disclosure T.E. Kelly: None. M.W. Beresford: None. </jats:sec

Parents of Children with Disabilities in the Early Months of COVID-19: Knowledge, Beliefs and Needs

COVID-19 has impacted families across the world. Besides the huge task of keeping their children and themselves healthy, families had more responsibilities such as supporting their children’s learning at home when they could not go to school. We asked 457 parents of children with disabilities about their knowledge, beliefs, and needs during the first few months of the pandemic. The parents reported a decrease in formal supports available to them. They also reported a decrease in being able to access informal supports. The parents stated concerns about the health and well-being of their families, the loss of jobs and income, delays and changes in special education services, and lack of technology to access special education from home. Their highest need was education for their children, followed by a need for family supports. High anxiety levels were also reported by most parents

Cost-Effectiveness of 2009 Pandemic Influenza A(H1N1) Vaccination in the United States

Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted.For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000-$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination

Ghosts of Landuse Past: Legacy Effects of Milldams for Riparian Nitrogen (N) Processing and Water Quality Functions

Milldams and their legacies have significantly influenced fluvial processes and geomorphology. However, less is known about their effects on riparian zone hydrology, biogeochemistry, and water quality. Here, we discuss the potential effects of existing and breached milldams on riparian nitrogen (N) processing through multiple competing hypotheses and observations from complementary studies. Competing hypotheses characterize riparian zone processes that remove (sink) or release (source) N. Elevated groundwater levels and reducing soil conditions upstream of milldams suggest that riparian zones above dams could be hotspots for N removal via denitrification and plant N uptake. On the other hand, dam removals and subsequent drops in stream and riparian groundwater levels result in drained, oxic soils which could increase soil nitrification and decrease riparian plant uptake due to groundwater bypassing the root zone. Whether dam removals would result in a net increase or decrease of N in riparian groundwaters is unknown and needs to be investigated. While nitrification, denitrification, and plant N uptake have typically received the most attention in riparian studies, other N cycle processes such as dissimilatory nitrate reduction to ammonium (DNRA) need to be considered. We also propose a novel concept of riparian discontinuum, which highlights the hydrologic and biogeochemical discontinuities introduced in riparian zones by anthropogenic structures such as milldams. Understanding and quantifying how milldams and similar structures influence the net source or sink behavior of riparian zones is urgently needed for guiding watershed management practices and for informed decision making with regard to dam removals

Operationalizing the Reciprocal Engagement Model of Genetic Counseling Practice: a Framework for the Scalable Delivery of Genomic Counseling and Testing

With the advent of widespread genomic testing for diagnostic indications and disease risk assessment, there is increased need to optimize genetic counseling services to support the scalable delivery of precision medicine. Here, we describe how we operationalized the reciprocal engagement model of genetic counseling practice to develop a framework of counseling components and strategies for the delivery of genomic results. This framework was constructed based upon qualitative research with patients receiving genomic counseling following online receipt of potentially actionable complex disease and pharmacogenomics reports. Consultation with a transdisciplinary group of investigators, including practicing genetic counselors, was sought to ensure broad scope and applicability of these strategies for use with any large‐scale genomic testing effort. We preserve the provision of pre‐test education and informed consent as established in Mendelian/single‐gene disease genetic counseling practice. Following receipt of genomic results, patients are afforded the opportunity to tailor the counseling agenda by selecting the specific test results they wish to discuss, specifying questions for discussion, and indicating their preference for counseling modality. The genetic counselor uses these patient preferences to set the genomic counseling session and to personalize result communication and risk reduction recommendations. Tailored visual aids and result summary reports divide areas of risk (genetic variant, family history, lifestyle) for each disease to facilitate discussion of multiple disease risks. Post‐counseling, session summary reports are actively routed to both the patient and their physician team to encourage review and follow‐up. Given the breadth of genomic information potentially resulting from genomic testing, this framework is put forth as a starting point to meet the need for scalable genetic counseling services in the delivery of precision medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147027/1/jgc41111.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147027/2/jgc41111-sup-0001.pd

Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200&nbsp;kilobases (kb), including a genome of 735&nbsp;kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Staying InformED: Top emergency Medicine pharmacotherapy articles of 2020

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The year 2020 was not easy for Emergency Medicine (EM) clinicians with the burden of tackling a pandemic. A large focus, rightfully so, was placed on the evolving diagnosis and management of patients with COVID-19 and, as such, the ability of clinicians to remain up to date on key EM pharmacotherapy literature may have been compromised. This article reviews the most important EM pharmacotherapy publications indexed in 2020. A modified Delphi approach was utilized for selected journals to identify the most impactful EM pharmacotherapy studies. A total of fifteen articles, eleven trials and four meta-analyses, were identified. This review provides a summary of each study, along with a commentary on the impact to the EM literature and EM clinician

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota.

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts