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This chapter explores one Canadian college's recent successes in distributed learning and technology utilization in program delivery during the outbreak of the COVID-19 pandemic. Following an appreciative inquiry approach, it discovers best/proven practices and dreams of what could be in shifting from traditional onsite applied learning to an integrated model of distributed learning. These practices and dreams, described with specific examples from students and faculty, are compiled into recommendations for future application. The five main recommendations are consistent delivery standards, communication and instructor availability, test/assignment flexibility, creative student engagement, and effective technology utilization. In addition, a key benefit realized by the appreciative inquiry was faculty and student engagement in identifying and implementing positive solutions for the future. © Springer Nature Switzerland AG 2021. All rights reserved.
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Background: Neutrophil serine proteases (NSPs) are involved in the pathogenesis of COVID19 and are increased in severe and fatal infection. We investigated whether treatment with Brensocatib, an inhibitor of dipeptidyl peptidase-1, an enzyme responsible for the activation of NSPs, would improve outcomes in hospitalized patients with COVID19. Method(s): In a randomized, double-blind, placebo-controlled trial, 406 hospitalized patients with COVID19 with at least one risk factor for severe disease were randomized 1:1 to once-daily Brensocatib 25mg (n=192) or placebo (n=214) for 28 days. Primary outcome was the 7-point World Health Organisation Clinical Status scale at day 29. Secondary outcomes included time to clinical improvement, national early warning score, new oxygen and ventilation use, neutrophil elastase activity in blood and mortality. Finding(s): Brensocatib treatment was associated with worse clinical status at day 29 (adjusted odds ratio 0 72, 95%CI 0 57-0 92) compared to placebo. The adjusted hazard ratio (aHR) for time to clinical improvement was 0 87 (95%CI 0 76-1 00) and time to hospital discharge was 0 98 (95%CI 0 84-1 13). During the 28-day follow-up period, 23 (11%) and 29 (15%) patients died in the placebo and Brensocatib treated groups respectively). Oxygen and new ventilation use were greater in the Brensocatib treated patients. Neutrophil elastase activity in blood was significantly reduced in the Brensocatib group from baseline to day 29. Prespecified subgroup analyses of the primary outcome supported the primary results.
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Introduction: COVID19 can cause neutrophilic inflammation and reaction oxygen species (ROS) production, leading to acute lung injury and mortality. AMPK is a key regulator of cellular energy with profound effects on neutrophil function. This study aims to investigate the role of AMPK activity in neutrophils during COVID-19 and pneumonia caused by pathogens other than SARS-CoV-2. Method(s): Patients hospitalised due to pneumonia or COVID-19 were recruited from Ninewells Hospital (Dundee, UK). Blood was sampled at day 1, 8, and 15. ROS production, phospho-AMPK (pAMPK), and NQO1 were stained in neutrophils, and then analysed by flow cytometry. The endogenous AMPK inhibitor, resistin, was quantified by ELISA, in serum (day 1, 8, 15). WHO clinical scale and CURB65 score were utilised to define severity. Result(s): 133 patients were enrolled (mean age 63.6 years). Resistin was not different between pneumonia and COVID-19 on day1. However, day 1 resistin was higher in severe disease defined by CURB65 Score (p=0.0220) and WHO score (p=0.0184). Resistin reduced over time at day 1 (mean 63.1pg/mL;n=121) to day 15 (mean 59.5pg/mL;n=66)(p=0.0002). Zymosan stimulation significantly increases neutrophil ROS production (p<0.0001), and significantly decreases NQO1 (p<0.0001), but caused no changes with pAMPK. There were no changes in these markers over time. pAMPK significantly correlated with NQO1 in unstimulated neutrophils (p=0.0388), but not when stimulated with zymosan. There were no associations between resistin and pAMPK, and no difference in these markers between pneumonia and COVID-19 groups. Conclusion(s): Our study suggests resistin as a marker of severity and disease course in COVID-19, independent of neutrophil AMPK signalling.
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Introduction: SARS-CoV-2 infection has profound effects on endothelial and immune cell function and coagulation, and better understanding of these events in COVID-19 would allow for targeted cardiovascular treatment and followup. Method(s): Longitudinal observational study of patients with PCR-confirmed SARS-CoV-2 infection admitted to hospital at two UK sites. Patients were enrolled within 96 hours of admission, with sampling up to day 29. RNAstabilised whole blood was processed for mRNA sequencing. Gene expression levels were compared between patients who did and did not suffer a major cardiac event (MACE) from admission to 1-year post-hospitalization. Result(s): At day 1, in acute COVID-19, no differences in gene expression were observed between those with (n=23) and without (n=140) a MACE. However, 93 significant differentially expressed genes (DEGs;adjusted pvalue<0.05;Wald test with Benjamini-Hochberg correction) were identified at day 29 between patients who suffered a MACE (n=16) or not (n=85) post-hospitalization. Neutrophil elastase (ELANE), tissue factor pathways inhibitor (TFPI) and integrin subunit alpha-2 (ITGA2B) were significantly elevated in patients who suffered a MACE. Significantly enriched pathways associated with cardiovascular events included type I interferon signalling and neutrophil chemotaxis. Conclusion(s): COVID-19 patients who experienced a MACE demonstrated significant changes in peripheral blood transcriptome 29 days after hospital admission. Significant DEGs were related to neutrophil activity, coagulation and interferon signalling, suggesting a relationship between these pathways and increased cardiovascular risk.
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Introduction and ObjectivesNeutrophils are increasingly recognised for a role in acute COVID19, contributing to hyperinflammatory responses, immunothrombosis and tissue damage. However, less is known about the cellular changes occurring within neutrophils in acute disease, as well as neutrophil function in patients recovering from COVID19. Mass spectrometry-based proteomics of neutrophils from hospitalised COVID19 patients sampled longitudinally was utilised to characterise these cells in both acute and long COVID19 (i.e. symptoms for ≥4 weeks).MethodsProspective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May 2020–December 2020). Patients were enrolled within 96 hours of admission, with longitudinal sampling up to day 29. Control groups comprised hospitalised patients with non-COVID19 acute respiratory infection and age-matched non-infected controls. Neutrophils isolated from peripheral blood were processed for mass spectrometry. COVID19 severity was defined using the WHO 7-point ordinal scale.Results84 COVID19 patients were included (mean age±SD 65.5±14.6 years;52.4% male), 91 non-COVID19 respiratory infection patients (age 65.7±16.7 years;49.5% male) and 42 non-infected controls (age 58.5±17.9;40% male). 1,748 proteins were significantly different (q-value≤0.05) in COVID19 neutrophils compared to those of non-infected controls. Major differences included a robust interferon response at baseline, with markers of neutrophil immaturity (CD10, CD71), increased neutrophil activation (CD64), and changes in metabolism which associated with COVID19 disease severity. Delayed recovery (WHO score 2–3) at day 29 was associated with significant changes in 1,107 proteins compared to the control population. Features of non-recovery included significantly reduced abundance of migratory receptors (e.g. C3AR1, LTB4R), integrins (CD11b, CD18), inhibitory molecules (e.g. SHP-1, SHIP-1) and indications of increased activation (CD64). Overall, ficolin and specific granule content was decreased in COVID19 patient neutrophils at day 29 compared with controls, however, comparing those who had recovered and those who had not, granule content was found to be significantly lower in the non-recovery group.ConclusionNeutrophils undergo significant changes in acute COVID19 associated with disease severity. Neutrophil proteomics revealed that these cells may have an ongoing role in non-recovered patients, including profiles associated with increased potential for neutrophil activation and reduced migratory capacity, highlighting neutrophils as potential therapeutic targets in long COVID19.
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Background With changes in NHS commissioning which aim for greater integration across larger areas and increased resourcing pressures experienced by hospices;strategic partnerships between hospices have never been more necessary. The recent Hospice UK Future Vision Programme (2020) set out principles of sustainability for hospices, many of which can be best achieved by working together. In 2017 our two hospices established a partnership;managed through a memorandum of understanding (MOU), it set out a shared ambition, agreed principles for engagement and the partnership's governance structure. Aims The partnership agreed to:•Work together with integrity and probity for the benefit of patients and the public.•Improve outcomes and experiences through early collaboration and planning.•Deliver high-quality standards of patient care, consistently and equitably across the system.•Lead the way in strategic planning of services that are safe and sustainable•Identify/share opportunities for good practice in transparent and value-for-money partnership arrangements. Achievements so far/Results Our hospices have developed supportive relationships and regular communication between leadership teams, operational managers and boards. Working collaboratively in:•Joint external education delivery - sharing resources, contacts and income.•Rehabilitation - supporting development of one partner's service through senior leadership and joint occupational therapy post.•Fundraising - trialling a joint mass-participation event.•Retail - supporting personal development of new income generation director and establishing improvements for retail.•Commissioning -to support negotiations with commissioners and increase influence across integrated care system.•Medical support - sharing senior medical resource to support development/business continuity.•Bed capacity - sharing inpatient capacity during COVID-19 - related closures.•Staff wellbeing - shared health/wellbeing month funded by NHS England. Conclusions By working together, we've achieved service improvements, shared expertise, increased efficiency and maintained business continuity. We continue to look for opportunities to work together for the furtherance of our stated aims as outlined in the MOU.
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IntroductionCOVID-19 is reported to cause profound systemic inflammation. Anti-inflammatory treatments such as corticosteroids and anti-IL-6 receptor monoclonal antibodies reduce mortality. Identifying inflammatory biomarkers associated with increased morbidity and mortality may allow both prediction of outcomes and identification of further therapeutic targets.MethodsA prospective observational study of patients with PCR-confirmed SARS-CoV-2 admitted to a single centre in Dundee, UK. Patients were enrolled within 96 hours of hospital admission. 45 inflammatory biomarkers were measured in serum using the Olink Target48 proteomic-based biomarker panel. Additional markers were measured by ELISA/immunoassay and enzyme activity assays. Severe disease was defined as the requirement for non-invasive or mechanical ventilation or death within 28 days of admission. Discrimination between groups was evaluated using the area under the receiver operator characteristic curve (AUC).Results176 patients were included (mean age 64.9 years, SD 13.6), 101 were male (57.4%). 56 patients developed severe disease (31.8%), mortality was 16.5%. Using ROC analysis, the strongest predictors of severity (p<0.0001) were CCL7/MCP3 (AUC 0.78 95%CI 0.70–0.85), IL6 (0.73 95%CI 0.66–0.81), IL15 (0.73 95%CI 0.65–0.81), CXCL10/IP10 (0.73 95%CI 0.65–0.81). Further significant predictors of severity included CXCL11, IL10, CCL2/MCP1 and CSF2/GM-CSF. Predictors of mortality were CXCL10 (0.78 95%CI 0.69–0.86), IL6 (0.76 95%CI 0.67–0.85), IL15 (0.75 95%CI 0.66–0.84), IL10 (0.73 95%CI 0.64–0.82). Further significant predictors of mortality were CXCL9 and CCL7.ConclusionMultiple circulating biomarkers were identified which predicted disease severity and mortality in COVID19, indicating clinical value in measurement upon hospital admission to highlight high-risk patients. Associated biological processes for these proteins included anti-viral and interferon responses and immune cell chemotaxis. In particular, CCL7 and CXCL10, the strongest predictors of severity and mortality in this dataset, are key players in the cytokine storm and immune cell recruitment linked with COVID19. These chemokines are not currently therapeutic targets, highlighting key avenues for further clinical research.
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IntroductionCOVID-19 has been reported to induce a ‘cytokine storm’ distinct from other acute respiratory tract infections (LRTIs). Understanding the similarities and differences in inflammatory profiles between SARS-CoV-2 infection and other respiratory infections may aid diagnosis, as well as the potential to repurpose therapies such as steroids and anti-IL-6 receptor antagonists for other respiratory infections.MethodsA prospective observational study of patients in 3 groups 1) PCR confirmed SARS-CoV-2 infection, 2) community-acquired pneumonia (CAP) without SARS-CoV-2, and 3) controls hospitalized for reasons other than infection. Patients were enrolled from a single centre in Dundee, UK. Patients were enrolled within 96 hours of hospital admission. 45 inflammatory biomarkers were measured in blood using the Olink target proteomic based biomarker panel. Additional markers were measured by ELISA/immunoassay and enzyme activity assay as appropriate. Discrimination between groups was evaluated using the area under the receiver operator characteristic curve (AUC).Results294 patients were included (COVID-19 n=176, CAP n=76, controls n=42), mean age 64 (SD±15.2) and 150 subjects were male (51.0%). Using ROC analysis the most discriminating biomarkers for COVID-19 compared to CAP were CXCL-10 (AUC 0.84 95%CI 0.78–0.90 p<0.001), CCL-8 (0.87 95%CI 0.82–0.92, p<0.001), CCL-7 (0.84 95%CI 0.78–0.89, p<0.001), CXCL-11 (0.80 95%CI 0.73–0.88, p<0.001). Further biomarkers included IL-18, IL-7, IL-10 and IL-33. The most discriminating biomarkers for COVID-19 compared to controls were CXCL-10 (0.89 95%CI 0.85–0.93, p<0.001, CCL-7 (0.88 95%CI 0.83–0.92, p<0.001), CCL-8 (0.87 95%CI 0.82–0.92, p<0.001). Further biomarkers included IL-10, CXCL-11 and IL-18. IL-4 was significantly lower in COVID-19 patients compared to controls (0.27 95%CI 0.16–0.38, p<0.001). No significant difference in IL-6 was seen between COVID-19 and CAP (median 21.9pg/ml vs 19.8pg/ml,p=0.59).ConclusionDifferential markers of inflammation were identified between COVID-19, CAP and control samples, indicating distinct immunological pathways. The identification of a similar IL-6 signature between COVID-19 and CAP indicates that IL-6 targeting therapies currently being used to treat COIVD-19 may also be beneficial in the treatment of CAP.
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How has COVID shown us communities can work in partnership with organisations? This paper will share reflections from a COVID project in a hospice in the United Kingdom that aimed to ensure that people in the community remained as connected as possible to others and felt the 'presence' of care around them despite physical distancing measures. In the paper, we will explore how necessity and restrictions presented by COVID actually offered us an opportunity to trial a new partnership approach to working together to ensure that people at home or shielding were connected to the community. The challenges and speed of COVID measures and their impact on every day work meant certain principles of reciprocity and agency that underpin relationship building between organisations and community members became a default rather than were hard won. We will reflect on how the learning and opportunities arising from this project have helped us all learn about community action, including the challenges of innovating between communities and organisations. Aims or goal of the work: To establish a community- based response to COVID-19 pandemic by working in partnership;to establish a learning and experimentation platform for innovation around social models of care;to ensure that at a time of physical distancing people felt supported and cared for by the surrounding community. Design, methods, and approach taken: A community development/action approach was taken, emphasising working with community members, groups and colleagues in partnership, using a 'learning and reflection' approach rather than a training one. During this time, a looser programme management approach was taken to models and delivery systems, using volunteers in flexible roles and, rather than managing people, linking affiliated community members together with others whatever their need, skillset or experience. Working in partnership with other groups to share resources and knowledge, training, or liaising with community groups around COVID. Resourcing the response through funding applications so that to help people did not come with greater cost for community members. Results: We have observed a growing confidence in community members associated with this initiative around death, dying and loss, and confidence to help others. Emphasising learning rather than training has introduced a reflective approach where community members support others and introduce new subjects to discuss. We have had a rise in interest from colleagues in initiatives involving the community, with 4 new projects internally requesting community-based help within a couple of months. We have had a rise in community groups requesting support from us or partnership working with peer-peer bereavement, befriending, and other community-led initiatives around death, dying, and loss. Conclusion/lessons learned: Working with a sense of shared purpose and simple ideas about compassionate care for others during COVID is a key element for changing the way that institutions and community members can work together. Emphasising that anyone who is part of an institution is also part of a community helps to value the lived experience of staff and community members. Having people involved in initiatives that help them make their own connections via 'learning by doing' and reflecting on their actions might be a more strategic way to introduce changes than to introduce 'top-down changes';relational approaches that emphasise community skillsets work well for emphasising trust and respect, and lead to a more networked approach in the community.
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Background and aims: Compassionate Neighbours is a well-established compassionate communities movement initiated through a series of hospices in the south-east of the United Kingdom. When the Covid-19 pandemic hit, it brought death and dying into the living rooms of the nation and new requirements to drastically alter patterns of social contact. For many organisations, volunteering was immediately halted and perceived as being too risky. But what was also being thrust onto the front pages was people's wish to connect, to take local action and support those vulnerable on their street. The Compassionate Neighbours movement did not step back during Covid-19 and in fact grew in numbers of volunteers and connections. This presentation will describe the experiences of one Compassionate Neighbours hub in south-east London and how Covid-19 has altered the landscape for connections at the end of life. Approach taken: - Rapid reassessment of risk which led to routine volunteering being superseded by new flexible, responsive, and safe roles. - Overcoming barriers such as the need for face to face training, identification badges. - New models of connecting such as 'furlongteering' (short, time-limited volunteering options), virtual and telephone communication, deliveries, and practical support for vulnerable. - Early integration with local groups such as the grassroots mutual aid organisations. - Capitalising on the groundswell of interest in volunteering to grow numbers of Compassionate Neighbours. - Bringing a compassionate and experienced response to the fearful narrative on death and dying. Results: Referral numbers for volunteer support peaked during this time, with 2.6 times the number of referrals for the same quarter in 2019 (32 vs 84 referrals per quarter).