COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

BACKGROUND: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. METHODS: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. RESULTS: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. CONCLUSIONS: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality.

A feasibility randomised trial comparing therapeutic thoracentesis to chest tube insertion for the management of pleural infection: results from the ACTion trial

Background: Pleural infection has a considerable healthcare burden with an average hospital stay of 14 days. There have been no randomised trials on the use of therapeutic thoracentesis (TT) for initial pleural fluid drainage. Aim(s): To assess the feasibility of a full-scale trial of chest tube vs TT for pleural infection. The primary outcome was defined as the acceptability of randomisation (ad priori defined as successful if >=50% of eligible patients were randomised). Method(s): Adult patients admitted with a pleural effusion related to infection and meeting recognised criteria for drainage were eligible. Participants were randomised (unblinded) to chest tube insertion or TT. Patients were followed up at 90 days. Result(s): From September 2019 and June 2021, 51 patients were diagnosed with complex parapneumonic effusion/empyema. Eleven patients met the inclusion criteria for trial and 10 patients were randomised (91%). The COVID-19 pandemic had a significant impact on recruitment. Patients randomised to TT had a shorter overall mean hospital stay (5.4 days, SD 5.1) compared to the chest tube control group (13 days, SD 6.0), p=0.04. Total number of pleural procedures required per patient were similar, 1.2 in chest tube group and 1.4 in TT group. No patients required surgical referral. Adverse events were similar between the groups with no readmissions related to pleural infection. Data completeness was high with no protocol deviations. Conclusion(s): The ACTion trial met its prespecified feasibility criteria for patient acceptability. The suggestion that TT can reduce hospital length of stay requires further investigation.

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: interim analysis of the DAYBREAK open-label extension study

Introduction: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of adults with either relapsing forms of multiple sclerosis (RMS) or moderately to severely active ulcerative colitis. Objective(s): To report the safety and efficacy of extended exposure to ozanimod from an ongoing open-label extension (OLE) trial. Method(s): Patients with RMS who completed a phase 1, 2, or 3 ozanimod trial were eligible to enrol in DAYBREAK (NCT02576717), where they received ozanimod 0.92 mg/d. The primary objective was to evaluate safety in the overall population;treatment-emergent adverse events (TEAE) were monitored. Efficacy was evaluated with annualised relapse rate (ARR), calculated via negative binomial regression and pooled for all parent-trial treatment groups. Number of new/ enlarging T2 and gadolinium-enhancing (GdE) magnetic resonance imaging (MRI) brain lesions were reported for patients who entered the OLE from an active-controlled phase 3 trial. Result(s): In total, 2639 patients completed the parent trials;this interim analysis (datacut 1 February 2022) included 2494 patients with mean (range) ozanimod exposure of 56.4 (0.03- 74.7) months (11732.2 patient-years) in the OLE. In the OLE, 2199 patients (88.2%) had any TEAE, 352 (14.1%) had a serious TEAE (SAE), and 89 (3.6%) discontinued due to a TEAE. Similar rates of TEAEs and SAEs occurred when assessed by parent trial treatment group. The most common TEAEs (based on preferred terms) were nasopharyngitis (20.6%), headache (16.9%), upper respiratory tract infection (11.9%), COVID- 19 infection (11.5%), and lymphopenia (10.5%), which were generally similar to parent trial observations (excluding COVID-19 infection). Adjusted ARR in the OLE was 0.099 (95% CI, 0.083-0.119). After 60 months of treatment, 68% of patients were relapse free in the OLE. Three- and 6-month confirmed disability progression was observed in 15.9% and 14.0% of patients in the OLE, respectively. Mean number of new/enlarging T2 lesions per scan at 60 months was similar, regardless of parent trial treatment group (range, 0.77-0.98), as was mean number of GdE lesions at month 60 (range, 0.057-0.065). Conclusion(s): The safety and tolerability profile of ozanimod in DAYBREAK was consistent with prior reports. Ozanimod treatment demonstrated sustained efficacy on clinical and MRI measures of disease activity and on disability progression.

MRI, efficacy, and safety of tolebrutinib in patients with highly active disease (HAD): 2-year data from the phase 2b Long-term safety (LTS) Study

Intoduction: In the phase 2b trial (NCT03889639), brain-penetrant Bruton's tyrosine kinase inhibitor tolebrutinib was well tolerated with dose-dependent reductions in new/enlarging MRI lesions. Objective/Aim: Report MRI, efficacy, and safety outcomes at Week (W)96 (2 years) of the phase 2b trial long-term safety (LTS) extension (NCT03996291) in relapsing MS patients with highly active disease (HAD). Method(s): In the double-blind portion of LTS (Part A), patients continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day). In the open-label Part B, all participants received 60 mg/day. HAD was defined as one relapse in the year prior to screening and one of the following: >1 gadolinium (Gd)- enhancing lesion within the prior 6 months, or >=9 T2 lesions at baseline (BL) or >=2 relapses in the prior year. Outcomes included Gd-enhancing and new/enlarging T2 lesions, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) score. Result(s): 61 patients met the HAD criteria at BL;60 continued in LTS Part A and 59 transitioned to Part B. As of 7 March 2022, 55 (92%) patients remained on study. New Gd-enhancing lesion counts remained low in the 60/60-mg arm through W96 and were reduced in other arms by W48 through W96, except for 5/60 at W96 (mean+/-SD at W96: 2.00+/-3.83, 0.56+/-1.04, 0.47+/-1.13, 0.23+/-0.44 in 5/60-, 15/60-, 30/60-, 60/60-mg arms, respectively). New/enlarging T2 lesion counts remained low for 15/60, 30/60, and 60/60 mg. T2 lesion volume remained unchanged for 60/60 mg. The most common treatment-emergent adverse events (TEAE) were COVID-19 (20%), nasopharyngitis (16.7%), headache (13.3%), and upper respiratory tract infection (8.3%). There was no dose-relationship for TEAE/serious AE in Part A and no new safety findings for patients switching to 60 mg in Part B. Of the patients who received tolebrutinib 60 mg/day for a minimum of 8 weeks, ARR was 0.10 (95% CI: 0.02, 0.66) and 92.9% remained relapse-free at W96. Mean EDSS scores were stable through W96. Conclusion(s): Through LTS Week 96, in the HAD cohort, tolebrutinib 60 mg demonstrated favourable safety (similar to the overall population), tolerability, and low ARR. New Gd-enhancing lesion counts remained low for the 60/60-mg arm.

COVID-19 infections and vaccinations among patients receiving ozanimod in the daybreak open-label extension trial

Introduction: COVID-19 emerged in late 2019. It is unclear whether selective sphingosine 1-phosphate (S1P) receptor modulators affect clinical outcomes of COVID-19 in patients with relapsing multiple sclerosis (RMS), including those who received SARS-CoV-2 vaccination. Objective(s): To characterise COVID-19 outcomes and vaccine breakthrough infections during ozanimod use, an S1P1 and S1P5 modulator, for treatment of RMS in an ongoing open-label extension (OLE) study. Method(s): DAYBREAK (NCT02576717), an OLE study of ozanimod 0.92 mg/d, began 16Oct2015. Patients who completed a phase 1-3 ozanimod RMS trial were eligible;>90% are from Eastern Europe. In this post hoc analysis, COVID-19 events from 1Nov2019 to 28Jan2022 in DAYBREAK were identified by MedDRA 24.1 COVID-19 SMQ (narrow scope). Each patient's most recent infection and all postvaccination infections were characterised. Result(s): Of 2181 patients in DAYBREAK during the analysis period, 319 (14.6%) developed COVID-19 (274 confirmed, 45 suspected). COVID-19 was nonserious in 291 (91.2%). During COVID-19, ozanimod was continued in 220 (69.0%) patients, interrupted in 94 (29.5%), and permanently discontinued in 3 (0.9%);action was unknown in 2 (0.6%) patients. At data cutoff, 285 (89.3%) had recovered (including 195 who had continued ozanimod), 6 (1.9%) recovered with sequelae, 5 (1.6%) were recovering, 16 (5.0%) had not recovered, and 5 (1.6%) died;a sixth COVID-19-related death due to lung abscess occurred after recovery with sequelae from COVID-19 infection. Of 1984 patients in DAYBREAK on 11Dec2020, when COVID-19 vaccines emerged, 596 (30.0%) received >=1 vaccine dose (415 [69.6%] mRNA;99 [16.6%] replication-defective viral vector;65 [10.9%] inactivated SARS-CoV-2;26 [4.4%] other);504 (25.4%) were fully vaccinated. COVID-19 occurred in 39/596 (6.5%) vaccinated patients and 213/1388 (15.3%) unvaccinated patients;3 postvaccination cases (including 1 case after 2 mRNA doses) were serious. Of 39 patients with postvaccination infections, 28 (71.8%) recovered (including 2/3 serious cases), 1 (2.6%) recovered with sequelae, 3 (7.7%) were recovering, and 7 (17.9%, including the third serious case) had not recovered at data cutoff. There were no COVID-19-related deaths among vaccinated patients. Conclusion(s): COVID-19 cases were largely nonserious, and the majority of infected patients recovered while continuing ozanimod. Few vaccinated patients developed COVID-19;most who did recovered without sequelae.

A multicentre, open label, single-arm, phase 3b study (CONSONANCE) to assess the effectiveness and safety of ocrelizumab in patients with primary and secondary progressive multiple sclerosis: year 2 interim analysis

Introduction: The approval of ocrelizumab (OCR) for the treatment of primary progressive MS (PPMS) showed that the course of progressive MS (PMS) can be altered with effective treatment;however, direct evidence across the spectrum of PMS, including secondary progressive MS (SPMS), is still lacking. Objective(s): CONSONANCE (NCT03523858) is a single-arm, phase 3b, 4-year study designed to evaluate for the first time the effectiveness and safety of OCR in patients with SPMS or PPMS. Year 2 results are reported. Method(s): Patients with active or non-active PMS but showing disability progression in the past 2 years were enrolled. Primary outcomes are (1) proportion of patients with no evidence of progression (NEP) defined as no progression confirmed for >=24 weeks on Expanded Disability Status Scale (EDSS), no >=20% increase in timed 25-foot walk test (T25FWT), no >=20% increase in nine-hole peg test (9HPT) time, and no MS-related death or treatment discontinuation due to efficacy failure;(2) proportion of patients with no evidence of progression and no active disease (NEPAD) defined as NEP plus no protocol-defined relapse, no new/enlarging T2 lesions (N/E-T2, re-baselined at week 24), and no T1 gadolinium-enhanced lesions. Result(s): Patients (n=629;SPMS n=324, PPMS n=305) had mean (SD) age of 48.5 (9.2) years and 52.3% were female. At baseline (BL), median (IQR)/mean (SD) EDSS scores were 6.0 (4.5- 6.0)/5.3 (1.3) for patients with SPMS and 5.0 (4.0-6.0)/4.8 (1.3) for PPMS. Overall median times for 9HPT and T25FWT were 27.9 and 9.4 seconds, respectively. Over 2 years, 311/586 (53.1%) patients had NEP (SPMS 55.8%;PPMS 50.2%;progression was mostly driven by increases in T25FWT) and 283/588 (48.1%) had NEPAD (SPMS 49.5%;PPMS 46.7%;acute activity predominantly driven by N/E-T2 lesions). Overall EDSS remained stable from BL to year 2 (mean [SD] change of +0.07 (0.79) points). In patients with EDSS >=2.0 at BL (n=526), 24-week confirmed disability improvement in any of the components (EDSS, T25FWT, 9HPT) was observed in 29.8% of cases. Rates of serious AEs and serious infections were 7.6/100PY and 3.2/100PY, respectively. Eight deaths were reported (COVID=6, pulmonary embolism=1, non-small cell lung cancer=1). Conclusion(s): Over a 2-year period, treatment with OCR was associated with comparable rates of NEP and NEPAD in patients with SPMS and PPMS, and with functional improvement in about one-third of patients. Safety outcomes were consistent with known safety profile.

ASCERTAINING THE RELATIONSHIP BETWEEN THE RADIOLOGIC TECHNOLOGISTS’ STANDARD PRECAUTION PRACTICES AND ATTITUDES IN HANDLING COVID-19 PATIENTS

Introduction Standard precautions are part of the infection control basis to protect radiology technologists from COVID-19 and other infections to prevent transmission from patient to patient and from healthcare workers to healthcare workers. This study ascertains the relationship between the standard practices and attitudes of radiologic technologists in handling COVID-19 patients. Methodology A quantitative-correlational design as used to specifically determine the standard precaution practices and attitudes of 46 radiologic technologists in the affiliated hospitals of the university, and the relationship of the two variables. Google form was used to gather data using the WHO Standard Precautions Protocol, which underwent pilot testing and a Cronbach alpha value of .804. Data analysis included descriptive statistics, Analysis of Variance (ANOVA) and Pearson-r correlation. Results The study revealed that radiologic technologists’ have high level of practices (μ=2.97 ±.0694) and attitude (μ=2.97 ±.824) in standard precaution. No significant difference was revealed in the standard precaution practices of radiologic technologists when grouped according to gender, years of service, age, and hospital type, Furthermore, no significant difference was revealed in the attitudes of radiologic technologist when grouped according to years of service, age, and hospital type, however, a significant difference was observed when the radiologic technologists were grouped according to gender (t (46) =2.04, p=.048) with female radiologic technologists having higher attitude (x̄=2.99, SD=.0253) on standard precautions than male radiologic technologists (x̄=2.94, SD=.0118). Overall, a high-positive correlation (r= .855, p=0.001) was revealed between the standard precaution practices and attitudes of radiologic technologists in handling COVID-19 patients. Conclusion There exist a good practice and good attitude in standard precaution of Radiologic technologists in handling COVID-19 patients and a very high-positive relationship between the two variables.

Safety/efficacy of evobrutinib, a Bruton's tyrosine kinase inhibitor, 2.5 years into Phase II MS open-label extension

Background and aims: Evobrutinib, a Bruton's tyrosine kinase inhibitor, was well tolerated and effective in a double-blind, randomised Phase II trial in patients with relapsing multiple sclerosis (pwRMS;NCT02975349). Objective: report evobrutinib safety and efficacy data 2.5 years into an open-label extension (OLE). Methods: In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily, W24), evobrutinib 25mg once-daily, 75mg once-daily, or 75mg twice-daily, or open-label dimethyl fumarate (DMF;240mg twice-daily). At W48 patients could enter the OLE (DMF: 4-8W washout);evobrutinib 75mg once-daily (median ∼48W) then 75mg twice-daily. We report the latest available OLE data. Results: Of 267 DBP patients, 213 (80%) entered the OLE;164 (61%) completed ≥132W OLE treatment. Treatmentemergent adverse events (TEAEs) were reported by 165/213 patients (77.5%);59 (27.7%) had a treatment-related TEAE (six were serious;Table). Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%);three (not treatment related;Covid pneumonia [n=2]) were fatal. Most patients had normal IgG (91%), IgA (88%) and IgM (82%) levels (OLE W120). Mean CD19+ B cells levels were 0.218x106cells/mL (OLE baseline) and 0.122x106cells/ mL (OLE W96). ALT/AST elevations only occurred in patients previously receiving DMF/evobrutinib 25mg, and within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, without clinical signs and symptoms. ARR, for patients receiving 75mg twice-daily in the DBP, was 0.12 (95%CI 0.07-0.20 [all available OLE data]). Conclusion: Evobrutinib safety and efficacy data over 2.5 years shows acceptable tolerability, no new safety signals and maintained efficacy in pwRMS.

Safety and Efficacy of Evobrutinib, a Bruton's Tyrosine Kinase Inhibitorin Relapsing Multiple Sclerosis Over 2.5 Years of The Open-Label Extension to a Phase II Trial

Objective: Report the safety and efficacy of evobrutinib over 2.5 years in an open-label extension (OLE). Background: Evobrutinib, a covalent, blood-brain barrier-penetrating Bruton's tyrosine kinase inhibitor, was well tolerated and effective at reducing gadolinium-enhancing lesions in a double-blind, randomized phase II trial in patients with relapsing multiple sclerosis (pwRMS;NCT02975349). Design/Methods: In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily at W24), evobrutinib 25mg once-daily, 75mg once-daily, or 75mg twice-daily, or open-label dimethyl fumarate (DMF;240mg twice-daily). At W48 patients could enter the OLE (DMF: 4-8W washout);evobrutinib 75mg once-daily (median ~48W) then 75mg twice-daily. The latest available OLE data are now reported. Results: Of 267 DBP patients, 213 (80%) entered the OLE;164 (61%) completed ≥132W of OLE treatment. Treatment-emergent adverse events (TEAEs) were reported by 165/213 patients (77.5%);59 (27.7%) had a treatment-related TEAE. Six serious TEAEs were deemed treatment-related. Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%);3 were fatal (Covid-19 pneumonia [n=2] and E. coli sepsis [n=1];not considered treatment-related). At OLE W120, most patients had IgG (91%), IgA (88%) and IgM (82%) within normal ranges. Overall mean CD19+ B cells levels were 0.218×10 cells/mL (OLE baseline) and 0.122×10 cells/mL (OLE W96). ALT/AST elevations were observed only in patients previously receiving DMF/evobrutinib 25mg and occurred within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, but without clinical signs and symptoms. Based on all available OLE data, ARR was 0.12 (95%CI 0.07-0.20) for patients receiving 75mg twice-daily in the DBP. 6 6 Conclusions: Evobrutinib safety and efficacy data over 2.5 years in pwRMS continue to show acceptable tolerability, with no new safety signals, and maintained efficacy.

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

Altered platelet proteome and platelet-leukocyte interactions in patients with COVID-19

Background: Patients with severe coronavirus disease 19 (COVID-19) are at increased risk of thrombosis, which is associated with enhanced coagulopathy and increased mortality. Previous studies showed enhanced platelet aggregation in patients with COVID-19, however the underlying mechanism and how this contributes to thrombosis is still unclear. Aims: To evaluate the platelet proteome, platelet functional responses and platelet/leukocyte aggregate formation in patients with COVID-19. Methods: This study was approved by the local ethics committee. Platelets were isolated from patients with COVID-19 and healthy controls after providing informed consent. Platelet lysates were subjected to tandem mass tag mass spectrometry (TMT-MS) proteomic analysis. Platelet functional responses such as integrin a IIb b 3 activation, P-selectin expression, platelet/leukocyte aggregates and PS exposure were analysed by FACS analysis. Results: The platelet proteome was altered in COVID-19, with enrichment of ribosomal and mitochondrial proteins, and reduced levels of thrombopoietin (TPO) receptor and signalling proteins. Circulating platelets from COVID-19 patients furthermore showed enhanced basal PS exposure, whereas basal integrin a IIb b 3 activation and P-selectin expression were unaltered. In contrast, agonist stimulated integrin a IIb b 3 activation and PS exposure were significantly decreased in COVID-19 patients. Furthermore, we found high levels of platelet/leukocyte aggregate formation in COVID-19 patients, which was reduced by a blocking anti-P-selectin antibody, suggesting immunothrombosis is part of the COVID-19 phenotype. Interestingly, however platelets in these platelet/leukocyte aggregates did not show enhanced integrin a IIb b 3 activation, suggesting they are generally in a low activation state, or having undergone activation followed by desensitisation. Conclusions: High levels of platelet/leukocyte aggregates are present and given the increased thrombotic tendency in severely ill patients, these findings point to an immunothrombotic pathogenesis. It will be important now to determine whether these changes are the result of direct activation of platelets or leukocytes by viral contact or cellular infection.

Achieving a multilevel evidence-based approach to improve cancer care in the U.S. post-COVID era: What is the role of management?

In 2013, the Institute of Medicine already had declared the state of U.S. cancer care as "a delivery system in crisis." Beginning in early 2020, the ongoing COVID-19 pandemic has dramatically revealed the fragile nature of the U.S. health system. As a microcosm of that larger health system, cancer care can provide us with opportunities for innovative thinking and new solutions. This paper describes a series of public and private-sector cancer care initiatives that are the building blocks for a multilevel evidence-based approach to improve cancer care in the post-COVID era. Achieving these objectives requires significant managerial policy decisions, some risk taking, and the development of organizational strategies that involve collaboration within the managerial and clinical leadership. Such strategies should reflect adaptability to navigate the complex and changing science, policy and financing environment, while retaining the central values of patient-centered care. As suggested by Edward Deming, an early pioneer in quality-improvement initiatives, the problems are with the system, and the system belongs to management. Though future challenges are undefined and likely to be significant, the foundational elements of a multilevel, evidence-based approach for improving cancer care are established and able to be built upon and will offer application in the post-COVID era.

COVID-19 and cancer: First report of the ESMO international, registry-based, cohort study (ESMO CoCARE)

Background: At the height of the first wave of the SARS-COV-2 pandemic, ESMO mobilized to accelerate research for the understanding of COVID-19 in cancer patients (pts). ESMO CoCARE is an international collaborative registry-based, cohort study, gathering real-world data and information from healthcare professionals about the natural history, treatment and outcomes of COVID-19 in cancer pts. Methods: ESMO CoCARE captures information on pts with any solid or hematologic malignancy (including cancer survivors free of disease for ≥5 years) presenting with a COVID-19 diagnosis in any of the participating centers. Data collected since 06/2020 include demographics, cancer characteristics and status, co-morbidities, COVID-19 clinical features, course, management and outcome. Factors influencing COVID-19 severity (hospitalization +/- ICU support needed) and recovery are investigated using multivariable logistic regression with backward elimination method. The study is ongoing. Results: The current analysis includes 1551 registered pts (19 countries;87% pts from 23 European centers, 7% and 6% pts from 5 Northern African and 7 Asian centers), with COVID-19 diagnosis as of 11/03/2021. Median age was 64 years, with the majority female (52%), cancer stage III/IV (58%), and on active cancer treatment (60%). 65% had severe COVID-19 requiring hospitalization, with 11% receiving intensive care. In multivariable analysis, in addition to demographics (male gender, older age, other ethnicity than Caucasian, lower BMI), co-morbidities and symptomatic COVID-19, severe disease was associated to higher ECOG PS (Odds Ratio (OR)2 vs 0=5.9, OR1 vs 0=2.1), hematological malignancies (OR hemvs solid =2.0), and active/progressive cancer status (OR progressivevs no evidence of disease =1.6). 98% of pts with mild disease recovered, as opposed to only 70% of those with severe disease. Cancer stage was an additional prognostic factor for recovery (ORI/II vs IV =3.4). Conclusions: Demographic characteristics, type and status of cancer, and symptomatology of COVID-19 increase the probability of severe disease, while advanced cancer stage is also associated with the risk of death. Legal entity responsible for the study: Institut Curie, Paris, France. Funding: ESMO - European Society for Medical Oncology. Disclosure: E. Romano: Financial Interests, Institutional, Funding, Investigator-initiated trial: AstraZeneca;Financial Interests, Institutional, Funding, Investigator-initiated trial: BMS;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Merck;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Pierre Fabre. R. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Funding: BMS. A. Croitoru: Financial Interests, Personal, Advisory Role: Ipsen;Financial Interests, Personal, Advisory Role: Astellas;Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb;Financial Interests, Personal and Institutional, Funding: Merck;Financial Interests, Personal and Institutional, Funding: Astellas;Financial Interests, Personal and Institutional, Funding: Servier;Financial Interests, Personal and Institutional, Funding: Five Prime Therapeutics;Financial Interests, Personal and Institutional, Funding: Amgen;Financial Interests, Personal, Other, Travel funding: Merck;Financial Interests, Personal, Other, travel funding: Servier;Financial Interests, Personal, Other, travel funding: Roche. S. Susnjar: Financial Interests, Personal, Other, Honoraria and/or advisory fees: Roche;Financial Interests, Personal, Other, Honoraria and/or advisory fees: Pfizer;Financial Interests, Personal, Other, Honoraria and/or advisory fees: Novartis;Financial Interests, Personal, Other, Honoraria and/or advisory fees: AstraZeneca;Financial Interests, Personal, Other, Honoraria and/or advisory fees: Amicus. M. Rossi: Financial Interests, Personal, Other, travel and personal fees: Novartis;Financial terests, Personal, Other, travel and personal fees: Ipsen. O.A. Michielin: Financial Interests, Personal, Other, personal fees: Bristol-Myers Squibb;Financial Interests, Personal, Other, personal fees: MSD;Financial Interests, Personal, Other, personal fees: Novartis;Financial Interests, Personal, Other, personal fees: Roche;Financial Interests, Personal, Other, personal fees: Amgen;Financial Interests, Personal, Other, personal fees: NeraCare GmbH. G. Pentheroudakis: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Lilly;Financial Interests, Personal, Advisory Board: Merck;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Institutional, Principal Investigator: AbbVie;Financial Interests, Institutional, Research Grant: Amgen;Financial Interests, Institutional, Principal Investigator, Coordinating PI: Amgen;Financial Interests, Institutional, Research Grant: AstraZeneca;Financial Interests, Institutional, Principal Investigator: AstraZeneca;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Funding: Boehringer Ingelheim;Financial Interests, Institutional, Funding: Bristol Myers Squibb;Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb;Financial Interests, Institutional, Principal Investigator: Debbiopharm;Financial Interests, Institutional, Funding: Enorasis;Financial Interests, Institutional, Funding: Genekor;Financial Interests, Institutional, Funding: Ipsen;Financial Interests, Institutional, Principal Investigator: Ipsen;Financial Interests, Institutional, Funding: Janssen;Financial Interests, Institutional, Principal Investigator: Lilly;Financial Interests, Institutional, Funding: Merck;Financial Interests, Institutional, Principal Investigator: Merck;Financial Interests, Institutional, Funding: MSD;Financial Interests, Institutional, Principal Investigator: MSD;Financial Interests, Institutional, Funding: Pfizer;Financial Interests, Institutional, Principal Investigator: Roche;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Institutional, Funding: Sanofi;Financial Interests, Institutional, Principal Investigator, Coodinating Pi: Servier;Financial Interests, Institutional, Funding: Servier. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, PharmaMar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody. Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda. Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. All other authors have declared no conflicts of interest.

Is convalescent plasma futile in COVID-19? A Bayesian re-analysis of the RECOVERY randomized controlled trial.

BACKGROUND: Randomized trials are generally performed from a frequentist perspective, which can conflate absence of evidence with evidence of absence. The RECOVERY trial evaluated convalescent plasma for patients hospitalized with coronavirus disease 2019 (COVID-19) and concluded that there was no evidence of an effect. Re-analysis from a Bayesian perspective is warranted. METHODS: Outcome data were extracted from the RECOVERY trial by serostatus and time of presentation. A Bayesian re-analysis with a wide variety of priors (vague, optimistic, sceptical, and pessimistic) was performed, calculating the posterior probability for: any benefit, an absolute risk difference of 0.5% (small benefit, number needed to treat 200), and an absolute risk difference of one percentage point (modest benefit, number needed to treat 100). RESULTS: Across all patients, when analysed with a vague prior, the likelihood of any benefit or a modest benefit with convalescent plasma was estimated to be 64% and 18%, respectively. The estimated chance of any benefit was 95% if presenting within 7 days of symptoms, or 17% if presenting after this. In patients without a detectable antibody response at presentation, the chance of any benefit was 85%. However, it was only 20% in patients with a detectable antibody response at presentation. CONCLUSIONS: Bayesian re-analysis suggests that convalescent plasma reduces mortality by at least one percentage point among the 39% of patients who present within 7 days of symptoms, and that there is a 67% chance of the same mortality reduction in the 38% who are seronegative at the time of presentation. This is in contrast to the results in people who already have antibodies when they present. This biologically plausible finding bears witness to the advantage of Bayesian analyses over misuse of hypothesis tests to inform decisions.

Learned helplessness and mental health issues related to distance learning due to COVID-19

When the COVID-19 pandemic struck in March 2020, universities worldwide were forced to suddenly move all in-person students online. In isolation and away from their regular structures and coping mechanisms, students were forced to rely on online learning technology (OLT) as a full replacement for in-person learning. We hypothesize that students in this circumstance will experience feelings of learned helplessness regarding OLT and suffer from overall poorer mental health. We present a mixed-methods study to investigate these phenomena during the Spring 2020 semester among a diverse group of students. We explore multiple factors that contributed to these phenomena, such as motivation, growing exhaustion with online learning, and feelings of connectedness that were lost and cannot be recreated via online meeting software. © 2021 Owner/Author.

Impact of the COVID-19 pandemic on management and outcomes in acute appendicitis: Should these new practices be the norm?

BACKGROUND: In early 2020, the COVID-19 pandemic significantly altered management of surgical patients globally. International guidelines recommended that non-operative management be implemented wherever possible (e.g. in proven uncomplicated appendicitis) to reduce pressure on healthcare services and reduce risk of peri-operative viral transmission. We sought to compare our management and outcomes of appendicitis during lockdown vs a non-pandemic period. METHODS: All presentations to our department with a clinical diagnosis of acute appendicitis between 12/03/2020 and 30/06/2020 were compared to the same 110-day period in 2019. Quantity and severity of presentations, use of radiological investigations, rate of operative intervention and histopathological findings were variables collected for comparison. RESULTS: There was a reduction in appendicitis presentations (from 74 to 56 cases), and an increase in radiological imaging (from 70.27% to 89.29%) (P = 0.007) from 2019 to 2020. In 2019, 93.24% of patients had appendicectomy, compared to 71.42% in 2020(P < 0.001). This decrease was most pronounced in uncomplicated cases, whose operative rates dropped from 90.32% to 62.5% (P = 0.009). Post-operative histology confirmed appendicitis in 73.9% in 2019, compared to 97.5% in 2020 (P = 0.001). Normal appendiceal pathology was reported for 17 cases (24.64%) in 2019, compared to none in 2020 (P < 0.001) - a 0% negative appendicectomy rate (NAR). DISCUSSION: The 0% NAR in 2020 is due to a combination of increased CT imaging, a higher threshold to operate, and is impacted by increased disease severity due to delayed patient presentation. This study adds to growing literature promoting routine use of radiological imaging to confirm appendicitis diagnosis. As we enter a second lockdown, patients should be encouraged to avoid late presentations, and surgical departments should continue using radiological imaging more liberally in guiding appendicitis management.

Internship commencement during COVID-19: the impact of an extended induction model.

BACKGROUND: The COVID-19 pandemic necessitated an enforced 8-week induction period (18 May to 12 July 2020) for all new interns in Ireland. These unprecedented circumstances presented a unique opportunity to assess this induction period. AIM: To assess the impact of a prolonged induction period on the technical abilities of interns embarking on their clinical careers. METHOD: We distributed a 12-item questionnaire to new interns at our institution during the COVID-19 pandemic. Section 1 of the questionnaire was designed to assess the rate of self-reported improvement in the successful and independent execution of practical 'intern' tasks. Section 2 of the questionnaire captured the subjective experience of interns during this time in relation to the effectiveness of an 8-week induction period with senior intern support available. Statistical analysis of categorical predictor and ordinal outcome variables was performed using the two-sample Wilcoxon rank-sum (Mann-Whitney) test. RESULTS: Our results demonstrated a statistically significant improvement in the proficiency at first attempt phlebotomy in week 8 compared with week 1 (p < 0.0001). There was a significant improvement in placing first-attempt peripheral IV lines in week 8 compared with week 1 (p < 0.001). Regarding the need for senior assistance, we demonstrated a statistically significant reduction in week 8 compared with week 1 (p = 0.046). There were 95.56% (n = 43) of interns that said they would recommend the induction period for future incoming interns. CONCLUSION: The COVID-19 pandemic has inadvertently identified a model of internship induction that benefits interns, their colleagues and their patients through the production of more technically capable interns.