Reflections on Developing Academic Identity During the Pandemic

This work is a post-modern autoethnographic reflexive narrative about the internal journey in the development of academic identity arising in the context of the transition from working as a casual academic to engagement for a short-term contract and beyond in the quest for tenure during the COVID-19 pandemic. It is an exploration of my personal story about moving from the periphery of academic belonging and being, to reaching the turning point going ‘over the bridge' toward the future cycles of becoming that await. This study highlights the importance of a sense of belonging and connection in the academic community as a foundation for being and future becoming. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Co-designing with engineers for community engagement in rural Uganda

Co-design is seen as crucial for designing solutions for resource-constrained people living in developing countries. To best understand their needs, user engagement and co-design strategies need to first be developed. In this Design Practice Brief, a process of co-design was created and used to understand ways telecommunication engineers could engage with rural communities in Uganda. It reports and reflects on (i) the experience of co-designing with nondesigners and (ii) creating a co-design structure and developing co-design methods of engaging with community members living in developing countries. In doing so, it offers a format and case study for future practitioners facilitating and conducting co-design with nondesigners and contributes to a knowledge gap in the reporting and reflection of co-design practice. This case study is unique as the co-design practice was achieved remotely (online), crossed disciplines (designers and telecommunication engineers) and cultural boundaries (European and African). It finds that in co-designing with nondesigners, preparation and structure are key, with acknowledgement and management of cultural and discipline differences.

Real world prospective evaluation of clinical outcomes in patients with non-metastatic castrate resistant prostate cancer treated with darolutamide

Background: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular informregarding use of next generation imaging in this setting. Method(s): Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Result(s): 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 -10) months. 42 patients (49.4%) had pre-treatment PSAdT of <6 months and 43 (50.6%) patients had PSAdT of >=6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT <6 months but median duration had not been reached for patients with pre-treatment PSAdT >=6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%);21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusion(s): In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of<6 months compared with>=6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study.

Metagenomic Next-Generation Sequencing of Plasma for Diagnosis of COVID-19-Associated Pulmonary Aspergillosis.

Timely diagnosis remains an unmet need in non-neutropenic patients at risk for aspergillosis, including those with COVID-19-associated pulmonary aspergillosis (CAPA), which in its early stages is characterized by tissue-invasive growth of the lungs with limited angioinvasion. Currently available mycological tests show limited sensitivity when testing blood specimens. Metagenomic next-generation sequencing (mNGS) to detect microbial cell-free DNA (mcfDNA) in plasma might overcome some of the limitations of conventional diagnostics. A two-center cohort study involving 114 COVID-19 intensive care unit patients evaluated the performance of plasma mcfDNA sequencing for the diagnosis of CAPA. Classification of CAPA was performed using the European Confederation for Medical Mycology (ECMM)/International Society for Human and Animal Mycoses (ISHAM) criteria. A total of 218 plasma samples were collected between April 2020 and June 2021 and tested for mcfDNA (Karius test). Only 6 patients were classified as probable CAPA, and 2 were classified as possible, while 106 patients did not fulfill CAPA criteria. The Karius test detected DNA of mold pathogens in 12 samples from 8 patients, including Aspergillus fumigatus in 10 samples from 6 patients. Mold pathogen DNA was detected in 5 of 6 (83% sensitivity) cases with probable CAPA (A. fumigatus in 8 samples from 4 patients and Rhizopus microsporus in 1 sample), while the test did not detect molds in 103 of 106 (97% specificity) cases without CAPA. The Karius test showed promising performance for diagnosis of CAPA when testing plasma, being highly specific. The test detected molds in all but one patient with probable CAPA, including cases where other mycological tests from blood resulted continuously negative, outlining the need for validation in larger studies.

Defective antifungal immunity in patients with COVID-19.

The COVID-19 pandemic has placed a huge strain on global healthcare and been a significant cause of increased morbidity and mortality, particularly in at-risk populations. This disease attacks the respiratory systems and causes significant immune dysregulation in affected patients creating a perfect opportunity for the development of invasive fungal disease (IFD). COVID-19 infection can instill a significant, poorly regulated pro-inflammatory response. Clinically induced immunosuppression or pro-inflammatory damage to mucosa facilitate the development of IFD and Aspergillus, Mucorales, and Candida infections have been regularly reported throughout the COVID-19 pandemic. Corticosteroids and immune modulators are used in the treatment of COVID-19. Corticosteroid use is also a risk factor for IFD, but not the only reason for IFD in COVID -19 patients. Specific dysregulation of the immune system through functional exhaustion of Natural killer (NK) cells and T cells has been observed in COVID-19 through the expression of the exhaustion markers NK-G2A and PD-1. Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune dysfunction/imbalance are important risk factors for IFD. The COVID-19 pandemic has significantly increased the at-risk population for IFD. Even if the incidence of IFD is relatively low, the size of this new at-risk population will result in a substantial increase in the overall, annual number of IFD cases. It is important to understand how and why certain patients with COVID-19 developed increased susceptibility to IFD, as this will improve our understanding of risk of IFD in the face of future pandemics but also in a clinical era of increased clinical immuno-suppression/modulation.

A large outbreak of the Kappa mutation of COVID-19 in Cork, Ireland, April-May 2021.

BACKGROUND: In May 2021, the B.1.617 variant of SARS-CoV-2 emerged in Ireland, and both Delta and Kappa sub-lineages were initially deemed variants of concern (VOCs) on a precautionary basis. We describe a large outbreak of SARS-CoV-2 B.1.617.1 (Kappa mutation) linked to a private gathering among third level students in Cork, Ireland. METHODS: Surveillance data were available from the Health Service Executive COVID Care Tracker. The epidemiological sequence of infection for each new case in this outbreak was tracked and whole genome sequencing was requested on all linked cases. Enhanced public health control measures were implemented by the Department of Public Health HSE-South to contain onward spread of VOCs, including retrospective contact tracing, lengthy isolation and quarantine periods for cases and close contacts. Extensive surveillance efforts were used to describe and control onward transmission. RESULTS: There were 146 confirmed SARS-CoV-2 cases linked to the outbreak. All sequenced cases (53/146; 36%) confirmed Kappa mutation. The median age was 21 years (range 17-65). The majority (88%) had symptoms of SARS-CoV-2 infection. There were 407 close contacts; the median was 3 per case (range 0-14). There were no known hospitalisations, ICU admissions or deaths. Vaccination data was unavailable, but the outbreak pre-dated routine availability of COVID-19 vaccines among younger adults in Ireland. CONCLUSION: Enhanced public health control measures for new and emerging variants of SARS-CoV-2 may be burdensome for cases and close contacts. The overall public health benefit of enhanced controls may only become apparent when evidence on disease transmissibility and severity becomes more complete.

Pulmonary rehabilitation online: current status and availability in 2022

BackgroundPulmonary rehabilitation (PR) is a core component of COPD treatment. An alternative to traditional face-to-face PR is online PR, also known as tele-rehabilitation. Despite lack of delivery standardisation there has been recent progression towards an online platform with myCOPD (NICE, 2022)1. The British Thoracic Society advising face-to-face PR suspension and COVID-19 restrictions may have encouraged services to develop tele-rehabilitation.MethodsA questionnaire survey of PR services in England explored the availability and practice of tele-rehabilitation in England. Additional aims were the investigation of recent development of tele-rehabilitation including changes following the COVID-19 pandemic, and potential barriers to and predictors of success for tele-rehabilitation delivery. The questionnaire used closed and open-ended questions and free text-boxes. Data was collected between 30th March 2022 and 19th April 2022.Results61 responses (33%) were received. 11 PR services (18%) stated that they had used a form of tele-rehabilitation prior to the COVID-19 pandemic and 59 (97%) services described using a form of tele-rehabilitation during COVID-19 restrictions. Common remote methods during COVID-19 restrictions included telephone (27%), videoconferencing with patients in groups (23%) and individual patient videoconferencing (21%).15 (25%) PR services strongly agreed, and 23 (38%) agreed, that inability to use tele-rehabilitation due to unfamiliarity with digital equipment or lack of access to the internet prevented many service users from using remote PR. 31 (51%) PR services strongly agreed, and 14 (23%) agreed, that face-to-face PR was preferred by users.31 (51%) PR services disagreed, and 13 (21%) strongly disagreed that tele-rehabilitation would be too costly whilst 7 (11%) strongly agreed, and 45 (74%) agreed that tele-rehabilitation would be beneficial to users.ConclusionTele-rehabilitation became widespread following COVID-19 restrictions, most commonly through telephone and videoconferencing. Most service users were thought to be unable to access tele-rehabilitation due to inability to access the internet and prefer face-to-face PR. Most services reported that cost was not an obstacle to tele-rehabilitation and would be beneficial to users.ReferencesNICE. (2022). Recommendations ;myCOPD for managing chronic obstructive pulmonary disease. [online] Available at: <https://www.nice.org.uk/guidance/MTG68/chapter/1-Recommendations> [Accessed 30 June 2022].

IMPACT OF THE COVID-19 PANDEMIC ON HOSPITAL ADMISSION RATE, LENGTH OF STAY, AND MORTALITY RATE FOR PATIENTS WITH COPD EXACERBATION: A RETROSPECTIVE STUDY

SESSION TITLE: COPD Assessment Tools and Comorbidities SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of hospital admissions. Coronavirus disease 2019 (COVID-19) has large impact on patients with pulmonary diseases. The purpose of the study is to evaluate the impact of COVID-19 on the following parameters for patients with COPD: Admission rate, length of stay, need for mechanical ventilation and all-cause mortality METHODS: Retrospective study with two cohorts, the first period is for patients admitted to the hospital with AECOPD before COVID-19 pandemic (01/01/2019 to 12/30/2019);the second period is for patients admitted with AECOPD since the beginning of COVID-19 pandemic (4/1/2020 to 3/31/2021). The length of stay (LOS), rate of patients requiring mechanical ventilation, and all-cause mortality were calculated and compared between two-groups of age, gender and comorbidities. RESULTS: There was a total of 55 (44.72%) patients in the pre-COVID period compared to 68 (55.28%) patients in the post-COVID period. In the pre-COVID period 16 (29.09%) patients were less than 60 year old and 39 (44.83%) patients were more than 60 year old. In the post-COVID period 39 (70.91%) patients were less than 60 year old and 48 (55.17%) patients were more than 60 year old. As for patients’ comorbidities, in pre-COVID period: 14 (19.44%) had hypertension, 26(36.11%) had diabetes, 27(37.50%) had ischemic heart disease, 3(4.17%) had myocardial infarction;in the post-COVID period: 20 (29.41%) had hypertension, 24(35.29%) had diabetes, 27(39.71%) had ischemic heart disease, 1(1.47) had myocardial infarction. The LOS was shorter in pre-COVID period compared to post-COVID period 6.51(SD 5.02) days vs 8.91(SD7.88) days with P-value of 0.042. The total number of patients needing mechanical ventilation in pre-COVID period was 3 (5.45%) compared to 3 (4.41%) in the post-COVID period with P-value of 0.555. All-cause mortality was 2 (3.64%) compared to 6 (8.82%) in post-COVID period with P-value of 0.217. CONCLUSIONS: Study result revealed significant difference in length of stay for patient with AECOPD where patient in post-COVID period had increased LOS compared to pre-COVID period. There was no significant difference in the number of patients, patients needing mechanical ventilation and all-cause mortality in between the two periods. CLINICAL IMPLICATIONS: The LOS in AECOPD is affected by multiple factors including underlying comorbidities, triggering factors for AECOPD and patient characteristics. Understanding these factors may help to optimize both patient care and health care utilization. Further studies are needed to assess the impact of COVID-19 on use of health care utilization for chronic pulmonary conditions such as COPD. DISCLOSURES: No relevant relationships by Omar Abdulfattah No relevant relationships by Zainab Alnafoosi No relevant relationships by Akshay Kohli No relevant relationships by Peter White

COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds.

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.

The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries

Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19-associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or cerebral involvement. Furthermore, a substantial proportion of patients who survived had life-changing morbidities (eg, loss of vision in 46% of survivors). Our Review indicates that COVID-19-associated mucormycosis is associated with high morbidity and mortality. Diagnosis of pulmonary mucormycosis is particularly challenging, and might be frequently missed in India.

Sustainable urban railways

The role of railways within urban areas is analysed, covering ‘metro’ systems (self-contained heavy rail networks, often with substantial underground sec-tions), light rail (both upgraded street tramways and newer systems), and travel by regional and national railways within urban areas. Basic operating characteristics, system capacity, capital costs, and technological change are examined. ‘Sustainability’ is analysed in respect of energy use and environmental impact, railways’ role in supporting high-density urban living (with associated benefits through greater use of non-motorised modes), and financial aspects (coverage of operating costs and ability to finance capital renewals). Current issues examined include the effect of users shifting to more flexible working patterns, the Covid pandemic, automation, and ownership. In general, urban railways can be seen to support a sustainable lifestyle, although some issues do arise in respect of longer distance commuting. © 2022 by Emerald Publishing Limited.

CT findings of COVID-19-associated pulmonary aspergillosis: a systematic review and individual patient data analysis.

PURPOSE: Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This study aims to conduct a systematic review and an individual patient-level image analysis of CT findings of COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: A systematic literature search was conducted to identify studies reporting CT findings of CAPA as of January 7, 2021. We summarized study-level clinical and CT findings of CAPA and collected individual patient CT images by inviting corresponding authors. The CT findings were categorized into four groups: group 1, typical appearance of COVID-19; group 2, indeterminate appearance of COVID-19; group 3, atypical for COVID-19 without cavities; and group 4, atypical for COVID-19 with cavities. In group 2, cases had only minor discrepant findings including solid nodules, isolated airspace consolidation with negligible ground-glass opacities, centrilobular micronodules, bronchial abnormalities, and cavities. RESULTS: The literature search identified 89 patients from 25 studies, and we collected CT images from 35 CAPA patients (mean age 62.4 ± 14.6 years; 21 men): group 1, thirteen patients (37.1%); group 2, eight patients (22.9%); group 3, six patients (17.1%); and group 4, eight patients (22.9%). Eight of the 14 patients (57.1%) with an atypical appearance had bronchial abnormalities, whereas only one (7.1%) had an angio-invasive fungal pattern. In the study-level analysis, cavities were reported in 12 of 54 patients (22.2%). CONCLUSION: CAPA can frequently manifest as COVID-19 pneumonia without common CT abnormalities of pulmonary aspergillosis. If abnormalities exist on CT images, CAPA may frequently accompany bronchial abnormalities.

Patient-reported outcomes of prepectoral implant-based breast reconstruction: Early results from the pre-bra prospective multi-centre cohort study

Introduction: Prepectoral breast reconstruction (PPBR) has been widely adopted due to a perceived reduction in post-operative pain and improved patient satisfaction but high-quality evidence to support these benefits is lacking. The Pre-BRA prospective multicentre cohort study aimed to explore the safety and effectiveness of PPBR prior to definitive evaluation in an RCT. Here we report the 1st analysis of the 18-month patient-reported outcome (PRO) data. Methods: Consecutive women undergoing PPBR at 40 UK centres were recruited to the Pre-BRA study between July 2019 and Dec 2020 with a 4 month pause to recruitment (March-July 2020) due to the COVID-19 pandemic. Demographic, operative, oncological, and 3-month safety data were collected. Women were asked to complete the BREAST-Q© (V2.0) at baseline, 3 and 18-months. Questionnaires were scored according to the developers' instructions and compared with the 18-month PRO results from the iBRA study which included mainly subpectoral mesh-assisted reconstruction. Results: 347 women underwent PPBR in the Pre-BRA study. Of these, 221 patients recruited pre-COVID have reached 18-month follow-up and 164 (74%) have completed the 18-month questionnaire. The median Satisfaction with Breasts score was 60 (48.5-71;0-100) [inter-quartile range;range] compared to 59 (48-71;0-100) in the UK iBRA study. Conclusions: Satisfaction with breasts at 18-months following surgery appears to be equivalent following pre and subpectoral breast reconstruction. Further analysis is needed, but this study supports the need for an RCT to definitively compare techniques and establish best practice for implant-based reconstruction.

Whose Outcome is it Anyway? Outcome and Brain Injury Case Management

Context: The acquired brain injury (ABI) literature highlights various factors that can prevent successful community rehabilitation and hinder good long-term outcomes. Brain injury case management is a service model with the potential to overcome these barriers within rehabilitation and longer-term care and support, but there is minimal research surrounding the effectiveness of case management in ABI. Objectives: This study aims to gain a better understanding of outcomes in brain injury case management and what facilitates good outcomes when working with clients from the perspective of brain injury case managers. Methods: A mixed qualitative study using both conventional content analysis and thematic analysis. Twenty-eight brain injury case managers completed an online questionnaire about what constitutes a good outcome in brain injury case management. Of these, five took part in a follow-up interview. Findings: The analysis identified four themes related to brain injury case management outcomes;1) A client-centred approach to outcome, 2) the role of the brain injury case manager, 3) monitoring outcome in case management, and 4) issues of funding. Limitations: Participation in the survey and interviews was somewhat low, largely due to conducting the study during the COVID-19 pandemic. The study only included brain injury case mangers and future studies should examine clients’ and family members’ perspectives. Implications: This study identified that brain injury case management is a holistic approach to rehabilitation and case coordination that requires further attention to develop evidence-informed practice. Appropriate holistic measures of quality of life and outcome need to be developed to support the evidence base for case management. © 2022 The Author(s).

Optimizing social and economic activity while containing SARS-CoV-2 transmission using DAEDALUS

To study the trade-off between economic, social and health outcomes in the management of a pandemic, DAEDALUS integrates a dynamic epidemiological model of SARS-CoV-2 transmission with a multi-sector economic model, reflecting sectoral heterogeneity in transmission and complex supply chains. The model identifies mitigation strategies that optimize economic production while constraining infections so that hospital capacity is not exceeded but allowing essential services, including much of the education sector, to remain active. The model differentiates closures by economic sector, keeping those sectors open that contribute little to transmission but much to economic output and those that produce essential services as intermediate or final consumption products. In an illustrative application to 63 sectors in the United Kingdom, the model achieves an economic gain of between £161 billion (24%) and £193 billion (29%) compared to a blanket lockdown of non-essential activities over six months. Although it has been designed for SARS-CoV-2, DAEDALUS is sufficiently flexible to be applicable to pandemics with different epidemiological characteristics. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

Determinants of turnaround time in a rapid genome sequencing program

Previous studies of genome sequencing (GS) in critically ill childrenhave made use of either modified hardware or working procedureswhich would be difficult, if not impossible, to integrate into existingclinical workflows1. Our lab’s transition from exome sequencing (ES) to GS offered an opportunity to implement in-house rapid genomesequencing (rGS) in critically ill children in a manner which couldintegrate with existing clinical workflows. We conducted a feasibilityand implementation pilot by offering rGS to child-parent triosconcurrently undergoing clinical rapid ES (rES) via a reference lab.The purpose of this study was to identify and address operationalbarriers to implementation of a rGS program capable of communicatinga preliminary result within 7 days of consent. We consideredthis time span to be more reflective of clinical realities than lab-quotedturnaround times (TAT) which typically start at sample receipt andthus do not account for challenges in sample acquisition and pre-testcounseling in a critical care setting, nor the impact of shipping times.Here we present data on TAT and lessons learned from the first 27subjects enrolled.Using rapid cycle improvement methodologies, we identified fourdistinct but inter-related workflows requiring optimization:1. Pre-analytic: patient identification through acquisition ofsamples2. Wet-lab: extraction through sequencing3. Bioinformatics: secondary and tertiary analysis as well as rapididentification of causal variants4. Return of resultsFigure 1 summarizes TAT across cases, demonstrating the markedimprovements in TAT with our programmatic approach to improvement.We used our first 9 cases to determine a baseline TAT for theentire process and to delineate the 4 main workflows (above). Atbaseline, excluding cases delayed by COVID-19 restrictions, mean TATwas 17.12 days (3 sequential deviant range: 7.05–27.19 days).Following deployment of our programmatic approach to rGS, meanTAT fell to 6.19 days (3 sequential deviant range: 0.51–11.87 days).Table 1 summarizes the observations and insights, by workflow, whichimpacted upon TAT and/or implementation. The single biggest impacton TAT was optimization of bioinformatics by removing all manualsteps between starting sequencing and producing human interpretable,filtered, annotated output of high-priority variants for interpretation.The second biggest source of improvement was optimization ofthe sequencing itself as well as prioritizing sample processing for andaccess to sequencing runs. While variant ranking is helpful in identifying causal variants, in 9/10 cases with a diagnostic findingthe causal variant(s)were obvious to the study teamwithin minutes ofviewing the annotated variant list, regardless of variant rank. (Figure Presented) As time required for sequencing and analytic workflows fell, therelative contribution of other workflows to overall TAT shifted and itbecame more obvious that early identification and utilization of thisapproach is very important in lowering overall time to diagnosis(Figure 2). In 6/10 cases with a diagnostic finding, the initial approachof the clinical team was NOT rES (and thus patients were not eligiblefor rGS on a research basis). Had rGS been the initial diagnosticmodality chosen, a diagnosis could have been reached in a median 12days sooner (range 2–28 days). There were also several cases wheresequencing was delayed when one or both parents did not present tothe lab to provide a blood sample in a timely manner. Optimization ofsequencing or analytic workflows cannot meaningfully improveoutcomes either of these situations.Our findings suggest some important considerations for institutionsdeveloping or seeking to improve rapid sequencing programs for acuteand critically ill children: (Table Presented) • Optimization of computational resource utilization and phenotypecuration saves more time than improved variant filtering orprioritization.• Obtaining samples from parents is non-trivial.• Even trained geneticists may fail to recognize appropriatecandidates for rGS.