ABSTRACT
Background: Advances in computational methodologies have enabled processing of large datasets originating from imaging studies. However, most imaging biomarkers suffer from a lack of direct links with underlying biology, as they are only observationally correlated with pathophysiology. Purpose(s): To develop and validate a novel AI-assisted image analysis platform, by applying quantitative radiotranscriptomics that quantifies cytokinedriven vascular inflammation from routine CT angiograms (CTA) performed as part of clinical care in COVID-19. Method(s): We used this platform to train the radiotranscriptomic signature C19-RS, derived from the perivascular space around the aorta and the internal mammary artery in routine chest CTAs, to best describe cytokinedriven vascular inflammation, defined using transcriptomic profiles from RNA sequencing data from human arterial biopsies (A). This signature was validated externally in 358 clinically indicated CT pulmonary angiograms from patients with or without COVID-19 from 3 different geographical regions. Result(s): First, 22 patients who had a CTA before the pandemic underwent repeat CTA <6 months post COVID-19 infection (B). Compared with 22 controls (matched for age, gender, and BMI) C19-RS was increased only in the COVID-19 group (C). Next, C19-RS was calculated in a cohort of 331 patients hospitalised during the pandemic, and was higher in COVID-19 positives (adjusted OR=2.97 [95% CI: 1.43-6.27], p=0.004, D). C19-RS had prognostic value for in-hospital mortality in COVID-19, with HR=3.31 ([95% CI: 1.49-7.33], p=0.003) and 2.58 ([95% CI: 1.10-6.05], p=0.028) in two testing cohorts respectively (E, F), adjusted for clinical factors and biochemical biomarkers of inflammation and myocardial injury. The corrected HR for in-hospital mortality was 8.24 [95% CI: 2.16-31.36], p=0.002 for those who received no treatment with dexamethasone, but only 2.27 [95% CI: 0.69-7.55], p=0.18 in those who received dexamethasone subsequently to the C19-RS based image analysis, suggesting that vascular inflammation may have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0.61, p=0.0003) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways. Conclusion(s): We present the first proof of concept study that combines transcriptomics with radiomics to provide a platform for the development of machine learning derived radiotranscriptomics analysis of routine clinical CT scans for the development of non-invasive imaging biomarkers. Application in COVID-19 produced C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation, that predicts inhospital mortality and identifies people who will have better response to anti-inflammatory treatments, allowing targeted therapy. This AI-assisted image analysis platform may have applications across a wide range of vascular diseases, from infections to autoimmune diseases.
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The COVID-19 pandemic resulted in profound disruption to geography higher education. A pivot to online teaching required staff to rapidly adapt their practices to novel digital spaces. Whilst many studies have reported the different pedagogic approaches adopted, fewer have evaluated the resultant student learning experience. In this study, we aimed to create an evidence base regarding the benefits and challenges of online learning during the pandemic, mapped against the teaching, cognitive and social presences of the Community of Inquiry framework. We adopted a mixed-methods approach of online surveys (105 students) and focus groups (14 students), undertaken across two undergraduate geography programmes in a British university, exploring the benefits of asynchronous and synchronous online learning, and assessment and feedback strategies. We discovered flexibility in student work patterns and use of technology to facilitate engagement in learning. We also identified key challenges for students such as time management, maintaining motivation, engaging in online classes, and feeling part of an online learning community. We identify best practice in collaborative-constructivist online learning, so that in the event of any future remote pivot, or with sustained adoption of blended modes of delivery, we can achieve a high-quality student learning experience. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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In the face of COVID-19, innovation, adaptation, and learning from experience have all been crucial to meeting the needs of those who have been displaced. In order to respond to this new disease, the humanitarian community had to get familiar with COVID-19. It was understood from the beginning that basic hygiene precautions, such adequate handwashing, could aid in preventing its transmission. However, a lot of displacement settings lack the infrastructure needed to put household and community-level infection prevention and control (IPC) measures into place. They might also have inadequate governance structures for overseeing and maintaining WASH services. Some of the hardest-to-reach populations are found in displacement contexts like Ethiopia, Somalia, and South Sudan, where people lack the resources to defend themselves and deal with health threats. Disease vulnerability may be exacerbated by overcrowding and restricted access to proper WASH facilities. In the meantime, xenophobia and stigma can develop due to the fear surrounding COVID-19 as well as the dissemination of false information. As new information became available and lessons were discovered, IOM teams operating in these environments had to modify their Risk Communication and Community Engagement (RCCE) and IPC efforts. Any disaster response has traditionally included funding for capacity building for hygiene promotion to strengthen local responses, but COVID-19 demanded more localisation because of the absence of international travel. It demonstrated how supporting local structures can help solidify hygiene promotion capacities while obviating the requirement for a high degree of international assistance in the event of future outbreaks by highlighting considerable local capacity and willingness in some communities.
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INTRODUCTION: Conservative management with antibiotics was recommended by the UK Surgical Royal Colleges early in the COVID-19 pandemic as the first-line treatment for acute uncomplicated appendicitis. METHODS: This is a prospective single-centre cohort study of patients aged 16 years or over, diagnosed clinically and confirmed radiologically with acute appendicitis in a secondary care setting who were initially treated conservatively with antibiotics. The primary outcome was the response to conservative management with antibiotics. Secondary outcomes were: antibiotic duration; operative rates; surgical approach (open, laparoscopic or conversion to open); complication rates; COVID-19 positive rate; rates of readmission within 12 months; and length of hospital stay. RESULTS: A total of 109 patients were included in the study, 67 of whom were male. Median age was 37 (range 17-93) years. A further 28 patients were excluded because of a decision to manage operatively on the index admission or because of other diagnoses. Thirty-three patients (30.3%) had surgery on the index admission after failed conservative management and 15 (13.8%) had surgery on readmission. On histology, 32/48 patients (66.7%) had a diagnosis of complicated appendicitis and 18/48 (37.5%) had a confirmed appendicolith. CONCLUSIONS: There was a high readmission rate (47/109; 43.1%) for surgery, a radiological drain or conservative management within the first year following initial conservative management. There is a significant risk of recurrence of symptoms, particularly in the presence of an appendicolith. Laparoscopic appendicectomy should be the first-line treatment, with conservative management reserved for patients with acute uncomplicated appendicitis who are COVID-19 positive or have comorbidities.
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Background: Infection with SARS-CoV-2 triggers a thromboinflammatory response with widespread endothelial damage and micro-and macro-vascular thrombosis that is associated with impaired function of multiple organs. Mechanisms underlying the hyperacute innate response that drives coagulation and inflammation are incompletely understood. Several lines of evidence support a role for overactivation of complement. Aims: To better understand the involvement of complement in COVID-19. Methods: We prospectively studied 25 COVID-19 ICU-hospitalized patients for up to 21 days. Commercial ELISAs were used to quantify complement pathway proteins and activation markers in serum of the patients and 25 healthy controls. Correlative and regression analyses were performed to determine the predictive value of biomarkers, in terms of respiratory function and mortality. Results: On admission, all COVID-19 patients exhibited significantly increased serum levels of terminal products of complement activation, C5a and sC5b-9. C4d levels, reflecting activation via the classical/ lectin pathways, were variably increased. All patients had excess activation of the alternative pathway (AP) with significantly elevated levels of factor B activation fragments, Ba and Bb. This was associated with a significant reduction (∼25%) in FH, a negative regulator of the AP. Ba levels correlated strongly with serum creatinine, the latter being a strong predictor of in-hospital mortality in COVID-19. C5a, Ba, Bb and factor D (FD) were significantly associated with hypoxemia. C5a, Ba, and FD, but not D-dimer, were significant independent predictors of mortality. Notably, levels of all complement activation markers were sustained throughout the patients' ICU stays, a finding in contrast to serum levels of IL-6, C-reactive protein and ferritin, which were more variable. Conclusions: All severely ill COVID-19 patients have increased and persistent activation of complement, minimally mediated via the AP. Complement activation biomarkers may be valuable predictors of hypoxemia and mortality. Large-scale studies will reveal the relevance of these findings to thrombo-inflammation in acute and postacute COVID-19.
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Introduction: Accurate staging, biomarker identification, and high-fidelity processes of care are critical for evidence-based treatment of NSCLC. To this end, the Association of Community Cancer Centers (ACCC) conducted a national, multi-phase effort to identify and provide guidance on key issues related to optimal care for patients with stage III/IV NSCLC. Methods: The quality improvement (QI) initiative, guided by an expert steering committee, included 5 phases: 1: Site Selection;2: Topic Identification, Quality Measure Development & Education;3: Data Collection & Analysis;4: Implementation of Educational Intervention;5: Analyze & Repeat. After site selection, baseline data were collected to assess key areas (demographics and clinical features, biomarker testing, process of care) across all sites using standardized data collection instruments. Baseline data were reviewed with each project team and a QI topic was selected via planning tele-conferences. An onsite (or virtual) full-day workshop was conducted with multidisciplinary cancer team members, including invited expert faculty, to define goals and develop site-specific QI projects. The main objects were to implement process-level improvements and develop quantitative benchmarks. Follow-up data collection (quantitative, qualitative, and process-level) was specific to each project and site (some were modified due to COVID-19) and all sites provided follow-up data on biomarker testing. Statistical analyses included summary statistics, frequency tables, and chi-square tests. Results: In pre-implementation (baseline) data collected at the six sites from 2018-2019, median patient ages were 65-72 years;50% Stage III and 50% Stage IV. The race distribution of patients and proportions insured under Medicare, Medicaid, or commercial varied substantially across sites. Biomarker testing also varied in 2018-2019, with clinicians having requested testing for 48-94% of Stage IV patients (with four sites >80%). When biomarkers were evaluated, EGFR and ALK were included in 70-100% of tests, BRAF and ROS1 in 14-87% of tests, and NTRK testing was rare. PDL1 was evaluated in 40-97% of patients. Important process-level improvements were achieved with the QI projects in 2020. Two sites focused on immune-related adverse events (irAEs), conducting a clinician survey to assess gaps in knowledge and care around identification and management of irAEs and developing a patient questionnaire to identify early signs of irAEs. A site focused on clinical trial enrollment and education and established a referral partnership with an NCI-designed cancer center. Two sites focused on biomarker testing, making progress towards standardization. Interventions included creation of a process map for ordering, optimizing workflow by standardizing key elements and template order-sets, increasing liquid biopsy use, and implementing pathology-driven reflex testing at diagnosis. Three sites improved testing rates of Stage IV patients from baseline to follow-up (48% to 81%;67% to 100%;80% to 100%). When biomarkers were tested in 2020, the use of panel testing was 87% overall (>70% for every site). Liquid biopsy was used regularly at three sites, testing 23%, 25%, and 40% of patients. Conclusion: This initiative aided six cancer programs in improving processes of care for patients with stage III/IV NSCLC. Despite some COVID-19 disruption, participating sites remained committed to implementing changes around biomarker testing, well-coordinated care delivery, and symptom management. Keywords: biomarker testing, immune-related adverse events, Quality of Care
ABSTRACT
Introduction: AccessHope (AH) is a program developed initially by City of Hope to provide remote subspecialist input on cancer care for patients as a supplemental benefit for specific payers and employers. While offering several platforms, the leading one has been an asynchronous model of review of medical records followed by a detailed assessment of past and current management along with discussion of potential future options in a report sent to the local oncologist. The intent of this program is that the patient can continue to have most or all management in their home environment, with the input and support of a subspecialist in that tumor type available “on demand”. This summary describes an early period of development and growth of this service, focusing in cases of lung cancer, particularly relevant during the COVID-19 pandemic. Methods: Appropriate cases for the eligible “at risk” population were identified by a trigger list of cancer diagnoses associated with a significant degree of risk of poor outcomes that included non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Medical records were solicited from the local medical team, from which a summary narrative and chronology was developed by a team of nurses at AH. This was shared with a physician specialist in thoracic oncology from AH who wrote a summary report within several days that was sent to the local physician, followed by a direct discussion with the recipient. Using descriptive statistics, case metrics focusing on concordance with the current or proposed management plan were tracked, along with recommended changes and clinical trial options, as well as potential cost savings from suggested changes. Results: Over a 19-month period from 4/19 through 11/20, 110 cases were reviewed: 55% male, median age 62.5 yrs (range 33-92);82% NSCLC (12% stage I/II, 16% stage III, 57% stage IV) and 17% SCLC (4% limited, 14% extensive). Median turnaround time for send out of report of 5.0 days. The AccessHope review agreed with the proposed or ongoing treatment in 79 (72%) cases and disagreed in 31 (28%) cases. Even with general agreement in the treatment approach, specific additional recommendations were associated with evidence-based anticipated improvements in efficacy in 76 cases (65%) and improvement in potential for cure in 14 cases (12%, only feasible in patients with curable disease). Specific recommendations associated with cost savings were identified in 14 cases (12%), associated with a total cost savings of $2,096,859. Molecular testing was ordered rarely for SCLC;for NSCLC, NGS was strongly favored and more commonly associated with more advanced stage and non-squamous histology. Conclusion: We have implemented a novel program of asynchronous reviews of cases of patients with lung cancer by thoracic oncology subspecialists and have demonstrated the feasibility of completing reports for a growing volume over the course of the pandemic without requiring travel and enabling patients to receive their care close to home. More than a quarter of these case reviews include recommendations associated with evidence to support improved clinical outcomes, as well as potentially significant cost savings from low value practices unsupported by evidence. Keywords: remote care, pandemic, expert review