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1.
Gastroenterology ; 160(6):S-2, 2021.
Article in English | EMBASE | ID: covidwho-1595905

ABSTRACT

Introduction: Obesity is a major risk factor for severe coronavirus disease, and clinical evidence now supports the GI tract, in addition to the respiratory system, as a potential route for SARS-CoV-2 infection. Expression of viral entry factors ACE2, TMPRSS2, and CTSL have been detected along the human GI tract including gastric, ileal and colonic mucosa. It is unclear whether obesity confers increased susceptibility to initial SARS-CoV-2 infection, or what gut mechanisms in obesity predispose to vulnerability to SARS-CoV-2. Thus, we aimed to investigate, by single cell RNA-sequencing (scRNA-Seq) of human colonic mucosa, whether patients with obesity may be more susceptible to SARS-CoV-2 infection, by virtue of enhanced expression of SARS-CoV2 entry cofactors followed protein assessment in colon biopsies. Methods: We studied 19 patients: 10 lean (age 33±3y, BMI 23±1kg/m2, 90% female), and 9 with obesity (age 43±3y, BMI 36±1kg/m2, 89% female). Human colonic biopsies from lean (n=4 scRNA-Seq;n=6 validation) and obesity (n=6 scRNASeq;n=3 validation) participants were obtained by sigmoidoscopy. Biopsies were dissociated, and viable cells were FACS-isolated. Chromium-10X Genomics was used for scRNA-Seq library prep, followed by Illumina HiSeq4000 sequencing. COVID-19 entry factors displaying significant differential expression between lean and obesity were then validated for gene, and protein expression in the validation cohort using Illumina TruSeq, and quantitative immunofluorescence confocal microscopy, respectively. Results: The initial dataset analysis revealed sequencing of 59,653 cells, 705 million reads, at 127,000 reads per cell. The human colonic mucosa partitioned into 20 cell subsets (Fig1A,B), and 15 of the 20 clusters displayed detectable expression of at least one of the COVID-19 entry factors: TMPRSS2, CTSL, or ACE2 (Fig1C,D,E). Goblet cell expression of TMPRSS2 was increased 4.6-fold (p<0.05), stromal cell expression of CTSL was increased 1.2-fold (p<0.0001), and ACE2 expression was increased 1.27-fold (p<0.001) in crypt-top (CT) colonocytes of obesity compared to lean controls (Fig2A). Colonic overexpression of TMPRSS2 mRNA (p<0.05) and protein (p<0.05), and CTSL (p<0.05) mRNA, but not ACE2 mRNA, in obesity was further validated in a second validation cohort (Fig2B-F). Conclusions: scRNA-Seq analysis of human colonic epithelium in obesity compared to healthy controls revealed multiple epithelial cell subsets (goblet cell, stromal, and colonocytes) with overexpression of COVID-19 entry factors TMPRSS2, CTSL, and ACE2, confirming the digestive system as a portal for infection by SARS-CoV-2.Furthermore goblet, stromal, and colonocyte-specific overexpression of TMPRSS2, CTSL, and ACE2 in obesity may play a significant role in increased initial susceptibility to COVID-19, and worse disease outcomes in human obesity.(Figure Presented) Single-Cell RNA-Seq Profiling of Human Colonic Epithelium in Obesity. A) t-SNE plot of single-cell RNA-seq profiles of native human colonic epithelial cells, colored by cluster number and identity, listed by largest to smallest population, and annotated by cluster identity, determined by highest ranking gene marker for the colonic cells clustered and profiled between lean and obesity, where dotted blue, red, and green circles represents goblet cells, stromal cells, and CT colonocytes, respectively. B) Proposed cluster identities based on conserved expression of known markers for annotated cell types. Clusters identified displayed expression of at least one of the COVID-19 entry factors: TMPRSS2, CTSL, or ACE2. The average proportion of cells in annotated clusters expressing, C) TMPRSS2, D) CTSL, and E) ACE2 among all studied participants.

2.
Clinical Lymphoma, Myeloma and Leukemia ; 21:S2-S3, 2021.
Article in English | EMBASE | ID: covidwho-1517533

ABSTRACT

Background: The role of upfront ASCT for NDTE MM remains under evaluation with high MRD rates following novel induction and consolidation (cons) strategies. K maintenance represents an alternative strategy to lenalidomide maintenance. The CARDAMON trial investigated K maintenance following KCd induction plus either ASCT or KCd cons. Methods: NDTE pts received 4 x KCd induction (K 20/56 mg/m2 biweekly, C 500 mg D 1,8,15, d 40mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons followed by 18 cycles K maintenance (56mg/m2 D1,8,15). Flow cytometric MRD (10-5) was assessed post induction, pre-maintenance and at 6 months maintenance. Primary endpoints were ≥VGPR post induction and 2-year PFS from randomisation. Secondary endpoints included improvements in disease response and MRD conversion following ASCT/ cons and maintenance. Results: 281 patients were registered, with 218 randomised to either ASCT or cons. The median PFS for ASCT was not yet reached vs 3.4 years for cons, with cons failing to show non-inferiority (difference in 2-year PFS 6.5%, 70% CI 1.0% to 11.1%). 196 patients received K maintenance (99 ASCT, 97 cons), 17 remain on treatment. A median of 16 cycles (1-18) were given over a median of 15.9 months (0-21.5). COVID-19 led to maintenance treatment interruptions in 41 (8 ASCT, 6 Cons) and treatment discontinuation in 15 (9 ASCT, 6 Cons). The median K dose given was 50.6mg/m2 and was similar across both arms (51.2 vs 49.4mg/m2, p=0.03). K maintenance was discontinued for PD in 14.1% (ASCT) vs 22.7% (cons), and for adverse events (AEs) in 7.1% (ASCT) vs 4.1% (cons). Most common AEs were hypertension and infections and more ≥G3 AEs were noted in ASCT vs cons (p=0.01). Patient/ clinician withdrawals from maintenance were low but occurred more in the ASCT arm (9.1% vs 1%). MRD neg patients post ASCT/ Cons had a longer PFS than MRD pos (p=0.002);with a higher MRD neg rate in the ASCT arm (53.6% vs 35.1% in Cons, p=0.01). MRD neg patients at 6 months post maintenance also had longer PFS (p=0.004 cf MRD pos patients);again with higher MRD neg rates in the ASCT arm (58.1% ASCT vs 40.5% Cons, p=0.02). There was no difference in PFS for MRD neg patients according to treatment arm from PBSCH, post-ASCT/ Cons or 6 months maintenance timepoints. Overall, 27.8% of MRD pos patients converted to MRD neg post ASCT/ Cons with more converting with ASCT (39.1% ASCT vs 16.1%, p=0.004). 23.5% of MRD pos patients converted to neg during maintenance (30.6% ASCT, 17.8%: p=0.2). Maintenance of MRD negativity over the first 6 months was similar between ASCT and Cons arms (p=0.3). There was no evidence that the timing of achievement of MRD negativity impacted PFS. Conclusions: K maintenance at 56mg/m2 weekly was deliverable and tolerable, with continued higher MRD neg rates at 6 months post-ASCT compared to post-Cons. However more ≥G3 AEs and discontinuations for AEs/ patient choice were noted for K maintenance after ASCT.

3.
Technology, Knowledge and Learning ; 2021.
Article in English | Scopus | ID: covidwho-1411937

ABSTRACT

Following publication of the original article, the authors identified an error in Fig. 1. The correct Fig. 1 and its caption is given in this erratum. The original article has been revised. (Figure presented.). © Springer Nature B.V. 2021

4.
HemaSphere ; 5(SUPPL 2):571-572, 2021.
Article in English | EMBASE | ID: covidwho-1393371

ABSTRACT

Background: ASCT is standard of care in biologically fit, newly diagnosed MM (NDMM) patients (pts), offering deeper responses with prolonged progression free/overall survival and improved quality of life (QOL). However, with the UK's 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT for MM due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to pts' treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QOL. Aims: To provide a snapshot of how COVID-19 affected the MM ASCT service in a single UK institution, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. To gain insight into MM pts' understanding of their disease, initial therapy and ASCT, and their response to therapy changes. Methods: We collected data on 115 NDMM pts who had a stem cell harvest (PBSCH) for upfront ASCT from December 2019-January 2021. During this time, 3 national lockdowns led to the ASCT service being suspended twice (March-June 2020 and January-February 2021). 25 pts within this cohort underwent a semi-structured interview via telephone. Inductive and deductive framework analysis was utilised to determine key themes and subthemes. Results: Pts were discussed in multidisciplinary meetings and decisions taken to delay or defer ASCT based on pt fitness, disease risk and depth of response. 73 (63%) proceeded to ASCT and 42 (37%) were deferred indefinitely (ASCTdef). The 2 groups were similar in terms of gender, age and ISS, but there were more pts with adverse risk cytogenetics in the ASCT group (26% vs 12%). Both groups were predominantly treated with bortezomib-based induction;in 11/73 (15%) ASCT and 7/42 (16.7%) ASCTdef pts treatment was changed to an oral, lenalidomide- based regimen to reduce hospital attendances for parenteral therapy. Overall response to induction in the 2 groups was similar;97.3% and 95.2% and 3VGPR 59% and 52.4% in ASCT and ASCTdef pts respectively. 28/73 ASCT pts had no delay to ASCT and none received bridging chemotherapy;45/73 had delayed ASCT (median 11 months [5-17] from start of induction) of whom 31 were put on bridging chemotherapy. In the 42 ASCTdef pts, 5 relapsed within ≤6 weeks of PBSCH and received 2nd line therapy, 30 were put on holding chemotherapy (previously not offered in the UK) as per NHS England COVID-19 interim guidance and 7 remained treatment-free post-induction. Thematic analysis identified 6 overarching themes: a) psychological response to diagnosis and initial therapy, b) beliefs and opinions about the benefits of ASCT, c) perceptions of information provided about MM and ASCT, d) high levels of fear and anxiety around COVID-19 and e) feelings about ASCT disruption or delay due to COVID-19 f) perceptions of care. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment and devastation at COVID-related treatment delays (in spite of high anxiety about infection) and exceptionally high levels of trust in the transplant team.

5.
Strategic Corporate Communication in the Digital Age ; : 1-18, 2021.
Article in English | Web of Science | ID: covidwho-1327428

ABSTRACT

Institutions and organizations are increasingly using the digital media to communicate with stakeholders on a day-to-day basis and during crisis situations. Therefore, this chapter presents a bibliographic analysis on digital corporate communication technologies. The grounded theory's inductive approach was used to capture and interpret the findings from Scopus-indexed publications. The articles were scrutinized in their entirety, including their research questions, methodologies and interpretation of the findings. Afterwards, this contribution identifies the opportunities and challenges that emerged during an unprecedented coronavirus (COVID-19) outbreak. In conclusion, it implies that there is scope for institutions and organizations to incorporate digital and social media in their crises' communications and risk management plans. This will enable them to be in a better position to engage in credible and transparent dialogic communications with different stakeholders.

6.
Journal of Strategy and Management ; : 20, 2021.
Article in English | Web of Science | ID: covidwho-1273030

ABSTRACT

Purpose This research identifies the critical factors of online service delivery of electronic commerce (e-commerce) websites, including website attractiveness, website functionality, website security and consumer fulfillment during an unprecedented Coronavirus (COVID-19) pandemic. Design/methodology/approach A structured questionnaire was used to gather data from 430 online respondents who were members of popular social media groups. The survey instrument relied on valid and reliable measures relating to electronic service quality (e-SERVQUAL) to better understand the participants' satisfaction with shopping websites, as well as their loyal behaviors and word-of-mouth activities. Findings The findings reported that consumers valued the e-commerce websites' features and their consumer order fulfillment capabilities. These factors increase the consumers' satisfaction with online shopping experiences, generate repeat business, as well as positive reviews on social media. Research limitations/implications This study addresses a knowledge gap in academia. To date, little research has focused on the consumer order fulfillment aspect of e-commerce transactions and on after-sales of online businesses. Originality/value This contribution posits that e-commerce websites ought to be appealing, functional and offer secure transactions. More importantly, it suggests that merchants should consistently deliver personalized service in all stages of an online purchase, including after the delivery of the ordered products.

7.
British Journal of Haematology ; 193(SUPPL 1):157-158, 2021.
Article in English | EMBASE | ID: covidwho-1255353

ABSTRACT

Content: Introduction: Myeloma patients who have completed chemotherapy moved from an intensive period of interaction with healthcare professionals, to less frequent visits. At this time, they often struggle with disease burden, treatment side effects and age-related co-morbidities. Improved patient survival with novel therapies has resulted in increasing patient numbers in outpatient haematology clinics. Centralisation of services means that many patients travel long distances to maintain contact with their transplant centres because they value the access to new drugs and clinical trials, and expertise in management of transplant-related complications and relapse. Faced with growing numbers of patients in follow up with survivorship needs, a new patient-centred model of care is needed. Method: The Promoting Individualised Self-Management and Survivorship (PrISMS) clinic was designed for myeloma patients who are off treatment and in plateau phase. This remote clinic is staffed by a doctor, a nurse specialist and a physiotherapist, a multidisciplinary team (MDT) approach to holistic management centred on patient needs and providing consistent individualised physical activity and lifestyle advice. Two weeks before the consultation, patients complete a questionnaire about their concerns, symptoms and ways in which they would like to improve their health. This allows the MDT to prepare appropriate advice for each patient, ensuring efficient use of consultations. Patients are also required to have a blood test either locally or at University College London Hospital before the clinic. Results: From March 2019 to October 2020, 54 patients were enrolled into the pilot PrISMS clinic and 197 telephone or video consultations were held. The median call duration was 12 minutes. Most patients had their blood tests (89%) and questionnaires (84%) completed before the appointment. Patients needing closer monitoring or active treatment due to disease relapse (9/54) were referred immediately back to face-to-face clinics. 78% and 89% of patients received nurse specialist's and physiotherapist's advice respectively at any point in time, with 11 patients (20%) referred to local exercise programmes. Patients were signposted to survivorship tools such as online exercise videos and lifestyle mobile applications when appropriate. Patient feedback was positive, with 31 of the 36 surveyed patients (86%) agreed or strongly agreed that they felt more confident in self-managing myeloma after PrISMS consultations. 94% (34/36) agreed or strongly agreed that their concerns and symptoms were addressed, and 77% (28/36) gave an overall service rating of good or excellent. Thematic analysis of telephone feedback interviews with 22 participants revealed additional benefits of reduction in travel costs and time, substantially shorter clinic waiting times and reduction in associated psychological stress (Table 1). Conclusion: This new patient-centred model of care has been demonstrated to be safe and feasible, with good patient satisfaction. We hope that this MDT approach will empower patients, improve their clinical experience, and build trust in their clinical teams, as well as reducing patients' sense of isolation and vulnerability particularly in this time of COVID-19 crisis. Future work is needed to formally confirm its effects on patient reported outcome measures, safety and healthcare resource usage.

8.
International Journal of Quality and Service Sciences ; ahead-of-print(ahead-of-print):14, 2021.
Article in English | Web of Science | ID: covidwho-1254976

ABSTRACT

Purpose This study aims to present a systematic review on service quality in higher education. It discusses about the latest opportunities and challenges facing higher educational institutions (HEIs) following the outbreak of the coronavirus (COVID-19) pandemic. Design/methodology/approach The study relied on the grounded theory's inductive reasoning to capture, analyze and synthesize the findings from academic and non-academic sources. The methodology involved a systematic review from Scopus-indexed journals, from intergovernmental and non-governmental policy documents, as well as from university ranking sites and league tables. Findings The comprehensive review suggests that HEIs can use different performance indicators and metrics to evaluate their service quality in terms of their resources, student-centered education, high-impact research and stakeholder engagement. Moreover, this paper sheds light about the impact of an unprecedented COVID-19 on higher education services. Practical implications During the first wave of COVID-19, the delivery of higher educational services migrated from traditional and blended learning approaches to fully virtual and remote course delivery. In the second wave, policy makers imposed a number of preventative measures, including social distancing and hygienic practices, among others, on HEIs. Originality/value This timely contribution has synthesized the findings on service quality and performance management in the higher education context. Furthermore, it investigated the effect of COVID-19 on higher education services. It deliberates on the challenges and responses in the short/medium term and provides a discussion on the way forward. In conclusion, it implies that HEI leaders ought to embrace online teaching models and virtual systems, as they are here to stay in a post-COVID-19 era.

10.
HemaSphere ; 5(SUPPL 1):45-46, 2021.
Article in English | EMBASE | ID: covidwho-1240935

ABSTRACT

Myeloma patients who have completed chemotherapy move from an intensive period of interaction with healthcare professionals, to less frequent visits. At this time, they often struggle with disease burden, as well as treatment related toxicities and age-related co-morbidities. We previously reported from focus group interviews that patients need lifestyle support and advice to return to their pre-morbid social, psychological and economic functionality. Improved patient survival with novel therapies has resulted in increasing patient numbers in outpatient clinics. Centralisation of services means that many patients travel long distances to maintain contact with their transplant centre because they value the access to optimal treatment and clinical trials. Faced with growing numbers of patients in follow up with survivorship needs, we designed the Promoting Individualised Self- Management and Survivorship (PrISMS) clinic for myeloma patients who are off treatment and in plateau phase in early 2019. This remote clinic is staffed by a doctor, a nurse specialist and a physiotherapist, a multidisciplinary team approach to holistic management centred on patient needs and providing consistent individualised physical activity and lifestyle advice. Two weeks before the consultation, patients are required to have a blood test locally or at our hospital, and to complete a questionnaire about their concerns, symptoms and ways in which they would like to improve their health. We did not know at the time that such model of care would become especially pertinent as a result of the COVID-19 pandemic. From March 2019 to October 2020, we enrolled 54 patients into the pilot PrISMS clinic and held 197 telephone or video consultations. The median call duration was 12 minutes, with most patients having had their blood tests (89%) and questionnaires (84%) completed before the appointment. Patients needing closer monitoring or active treatment due to disease relapse (9/54) were referred immediately back to face-to-face clinics. 78% and 89% of patients received nurse specialist's and physiotherapist's advice at any point in time, with 11 patients (20%) referred to local exercise programmes. Regarding patients' feedback, 31 of the 36 surveyed patients (86%) agreed or strongly agreed that they felt more confident in self-managing myeloma after the consultations. 94% (34/36) of the survey patients agreed or strongly agreed that their concerns and symptoms were addressed, and 77% (28/36) gave an overall service rating of good or excellent. Thematic analysis of telephone interviews with 22 participants revealed additional benefits of reduction in travel costs and time, shorter waiting times and reduction in associated psychological stress (Table 1). PrISMS clinic aims to empower patients through patient-centred care by providing tailored advice, through enhancing patients' competences by signposting them to various survivorship tools (Table 2), and through active patient participation by setting achievable goals. We hope that this new care model will improve patients' clinical experience and build trust in their clinical teams particularly at this time of crisis, and to reduce their sense of isolation. We continue to evaluate this service based on patients' feedback to optimise individualised care and resource allocation. Future work is needed to formally confirm its effects on patient reported outcome measures, safety and healthcare resource usage. (Table Presented).

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