Background Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. Study and design This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. Conclusion The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.
descriptionPublicationkeyboard_double_arrow_right Article 2023American Association for Cancer Research (AACR)
Authors: Amanda J. Compadre; Lillian N. van Biljon; Mark C. Valentine; Alba Llop-Guevara; +19 Authors
Amanda J. Compadre; Lillian N. van Biljon; Mark C. Valentine; Alba Llop-Guevara; Emily Graham; Bisiayo Fashemi; Andrea Herencia-Ropero; Emilee N. Kotnik; Isaac Cooper; Shariska P. Harrington; Lindsay M. Kuroki; Carolyn K. McCourt; Andrea R. Hagemann; Premal H. Thaker; David G. Mutch; Matthew A. Powell; Lulu Sun; Nima Mosammaparast; Violeta Serra; Peinan Zhao; Elena Lomonosova; Dineo Khabele; Mary M. Mullen;
Biomarker predictive; Chemotherapy; Ovarian cancer Biomarcador predictiu; Quimioteràpia; Càncer d'ovari Biomarcador predictivo; Quimioterapia; Cáncer de ovario Purpose: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. Experimental Design: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. Results: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; P = 0.003) than RAD51-High status. Conclusions: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials. This work was supported by the following entities: M. Mullen reports funding from the Reproductive Scientist Development Program (RSDP) supported by the Gynecologic Oncology Group Foundation, Washington University School of Medicine Division of Physician Scientists Dean's Scholar Program, and grant 2021265 from the Doris Duke Charitable Foundation through the COVID-19 Fund to Retain Clinical Scientists collaborative grant program. D. Khabele reports funding from RO1CA243511, University of Kansas Cancer Center P30 CA168524. D.G. Mutch reports funding from Washington University School of Medicine grant 5U1-CA180860–04.
descriptionPublicationkeyboard_double_arrow_right Article , Other literature type 2021 United Kingdom, Belgium, Turkey Ovid Technologies (Wolters Kluwer Health) NHMRC | Precision treatment for m..., NHMRC | Precision therapy for neu...
NHMRC| Precision treatment for multiple sclerosis: Maximising the effect of immunomodulatory therapy ,
NHMRC| Precision therapy for neurological diseases
Authors: Steve Simpson-Yap; Edward De Brouwer; Tomas Kalincik; Nick Rijke; +43 Authors
Steve Simpson-Yap; Edward De Brouwer; Tomas Kalincik; Nick Rijke; J. Hillert; Clare Walton; Gilles Edan; Yves Moreau; Tim Spelman; Lotte Geys; Tina Parciak; Clément Gautrais; Nikola Lazovski; Ashkan Pirmani; Amin Ardeshirdavanai; Lars Forsberg; Anna Glaser; Robert N. McBurney; Hollie Schmidt; Arnfin Bergmann; Stefan Braune; Alexander Stahmann; Rodden M. Middleton; Amber Salter; Robert J. Fox; Anneke Van Der Walt; Helmut Butzkueven; Raed Alroughani; Serkan Ozakbas; Juan Ignacio Rojas; Ingrid van der Mei; Nupur Nag; Rumen Ivanov; Guilherme Sciascia do Olival; Alice Estavo Dias; Melinda Magyari; Doralina Guimarães Brum; Maria Fernanda Mendes; Ricardo Alonso; Richard S. Nicholas; Johana Bauer; Anibal Chertcoff; Anna Zabalza; Georgina Arrambide; Alexander Fidao; Giancarlo Comi; Liesbet M. Peeters;
Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Esclerosi múltiple Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Esclerosis múltiple Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Multiple Sclerosis Background and Objectives People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1–12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score. Results Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01–2.41; aOR 2.43, 95% CI 1.48–4.02) and ICU admission (aOR 2.30, 95% CI 0.98–5.39; aOR 3.93, 95% CI 1.56–9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54–10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29–2.38; aOR 2.76, 95% CI 1.87–4.07) and ICU admission (aOR 2.55, 95% CI 1.49–4.36; aOR 4.32, 95% CI 2.27–8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09–12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13–3.07; aOR 2.88, 95% CI 1.68–4.92) and ICU admission (aOR 2.13, 95% CI 0.85–5.35; aOR 3.23, 95% CI 1.17–8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71–17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity. Discussion Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. The operational costs linked to this study are funded by the Multiple Sclerosis International Federation (MSIF) and the Multiple Sclerosis Data Alliance (MSDA), acting under the umbrella of the European Charcot Foundation. The MSDA receives income from a range of corporate sponsors, recently including Biogen, Bristol-Myers Squibb (formerly Celgene), Canopy Growth Corp, Genzyme, Icometrix, Merck, Mylan, Novartis, QMENTA, Quanterix, and Roche. MSIF receives income from a range of corporate sponsors, recently including Biogen, Bristol-Myers Squibb (formerly Celgene), Genzyme, Med-Day, Merck, Mylan, Novartis, and Roche. This work was supported by the Flemish government under the Onderzoeksprogramma Artificiële Intelligentie Vlaanderen programme and the Research Foundation Fladers (FWO) for ELIXIR Belgium–Flanders (FWO) for ELIXIR Belgium. The central platform was provided by QMENTA, and the computational resources used in this work were provided by Amazon. The statistical analysis was carried out at CORe, The University of Melbourne, with support from the National Health and Medical Research Council (NHMRC; 1129189 and 1140766).
COVID-19; Cancer; End-of life care (EOLC) COVID-19; Cáncer; Cuidados al final de la vida COVID-19; Càncer; Cures al final de la vida Background: Specialist palliative care team (SPCT) involvement has been shown to improve symptom control and end-of-life care for patients with cancer, but little is known as to how these have been impacted by the COVID-19 pandemic. Here, we report SPCT involvement during the first wave of the pandemic and compare outcomes for patients with cancer who received and did not receive SPCT input from multiple European cancer centres. Methods: From the OnCovid repository (N = 1318), we analysed cancer patients aged ⩾18 diagnosed with COVID-19 between 26 February and 22 June 2020 who had complete specialist palliative care team data (SPCT+ referred; SPCT− not referred). Results: Of 555 eligible patients, 317 were male (57.1%), with a median age of 70 years (IQR 20). At COVID-19 diagnosis, 44.7% were on anti-cancer therapy and 53.3% had ⩾1 co-morbidity. Two hundred and six patients received SPCT input for symptom control (80.1%), psychological support (54.4%) and/or advance care planning (51%). SPCT+ patients had more ‘Do not attempt cardio-pulmonary resuscitation’ orders completed prior to (12.6% versus 3.7%) and during admission (50% versus 22.1%, p < 0.001), with more SPCT+ patients deemed suitable for treatment escalation (50% versus 22.1%, p < 0.001). SPCT involvement was associated with higher discharge rates from hospital for end-of-life care (9.7% versus 0%, p < 0.001). End-of-life anticipatory prescribing was higher in SPCT+ patients, with opioids (96.3% versus 47.1%) and benzodiazepines (82.9% versus 41.2%) being used frequently for symptom control. Conclusion: SPCT referral facilitated symptom control, emergency care and discharge planning, as well as high rates of referral for psychological support than previously reported. Our study highlighted the critical need of SPCTs for patients with cancer during the pandemic and should inform service planning for this population. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Wellcome Trust Strategic Fund [PS3416] awarded to DJP and by direct project funding from the NIHR Imperial Biomedical Research Centre (BRC) awarded to DJP. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. OnCovid was supported in part by funds from the Cancer Treatment and Research Trust (CTRT) awarded to DJP and from the Associazione Italiana per la Ricerca sul Cancro Foundation  awarded to AG.
COVID-19; Acute myeloid leukemia; Survey COVID-19; Leucemia mieloide aguda; Encuesta COVID-19; Leucèmia mieloide aguda; Enquesta Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible. EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by Gilead Science, USA (Project 2020-8223). The funder of the study had no role in the study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication.
Respiratory infections and tuberculosis Infecciones respiratorias y tuberculosis Infeccions respiratòries i tuberculosi Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55–78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5–19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6–23) days versus 8 (4–15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65–0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU. This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z), the Bill and Melinda Gates Foundation (OPP1209135), Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity OV2170359, grants from Rapid European COVID-19 Emergency Response Research (Horizon 2020 project 101003589), the European Clinical Research Alliance on Infectious Diseases (965313), The Imperial National Institute for Health Research (NIHR) Biomedical Research Centre, and The Cambridge NIHR Biomedical Research Centre; and endorsed by the Irish Critical Care Clinical Trials Group, co-ordinated in Ireland by the Irish Critical Care Clinical Trials Network at University College Dublin and funded by the Health Research Board of Ireland (CTN-2014-12). Data and Material provision was supported by grants from: the NIHR (award CO-CIN-01), the Medical Research Council (grant MC_PC_19059), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), Wellcome Trust (Turtle, Lance-fellowship 205228/Z/16/Z), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. This work was by Research Council of Norway grant number 312780, and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner.
Background Tracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective. Aim We demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters. Methods Genomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021. Results Cluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf. Conclusion IGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.
COVID-19 vaccine; Adverse drug reaction; Myocarditis Vacuna contra el COVID-19; Reacció adversa a fàrmacs; Miocarditis Vacuna contra el COVID-19; Reacción adversa a medicamentos; Miocarditis Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39–49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed. The project received support from the European Medicines Agency (EMA/2018/23/PE).
descriptionPublicationkeyboard_double_arrow_right Article , Other literature type 2022Embargo end date: 06 Jan 2022 Belgium, Switzerland English IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
The aim of this study was to investigate the COVID-19 vaccination acceptance rate and its determinants among healthcare workers in a multicenter study. This was a cross-sectional multi-center survey conducted from February 5 to April 29, 2021. The questionnaire consisted of 26 items in 6 subscales. The English version of the questionnaire was translated into seven languages and distributed through Google Forms using snowball sampling; a colleague in each country was responsible for the forward and backward translation, and also the distribution of the questionnaire. A forward stepwise logistic regression was utilized to explore the variables and questionnaire factors tied to the intention to COVID-19 vaccination. 4630 participants from 91 countries completed the questionnaire. According to the United Nations Development Program 2020, 43.6 % of participants were from low Human Development Index (HDI) regions, 48.3 % high and very high, and 8.1 % from medium. The overall vaccination hesitancy rate was 37 %. Three out of six factors of the questionnaire were significantly related to intention to the vaccination. While ���Perceived benefits of the COVID-19 vaccination��� (OR: 3.82, p-value<0.001) and ���Prosocial norms��� (OR: 5.18, p-value<0.001) were associated with vaccination acceptance, ���The vaccine safety/cost concerns��� with OR: 3.52, p-value<0.001 was tied to vaccination hesitancy. Medical doctors and pharmacists were more willing to take the vaccine in comparison to others. Importantly, HDI with OR: 12.28, 95 % CI: 6.10-24.72 was a strong positive determinant of COVID-19 vaccination acceptance. This study highlighted the vaccination hesitancy rate of 37 % in our sample among HCWs. Increasing awareness regarding vaccination benefits, confronting the misinformation, and strengthening the prosocial norms would be the primary domains for maximizing the vaccination coverage. The study also showed that the HDI is strongly associated with the vaccination acceptance/hesitancy, in a way that those living in low HDI contexts are more hesitant to receive the vaccine. EXCLI Journal; 21:Doc93; ISSN 1611-2156