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11.
A. Mohammed Idhrees Prasanna Karthik Suthakaran George Jose Valooran Mohamad Bashir 《The International journal of angiology》2021,30(2):155
Infection with the novel coronavirus, SARS-CoV2, produces the clinical syndrome COVID-19. COVID-19 is a systemic illness inducing hyperinflammation and cytokine storm affecting multiple organs including the myocardium which is reflected in elevated cardiac biomarkers such as troponin, lactate dehydrogenase, and creatinine kinase MB. Furthermore, COVID-19 has been implicated in increased predilection to thromboembolic phenomena. Hence, mortality in patients with associated cardiovascular disease has been higher compared with the cohort with no cardiovascular comorbidity. It is entirely unknown how remdesivir will change the facet of cardiovascular medicine and surgery. In the present constantly changing climate, this review of remdesivir and its association with cardiovascular disease is comprehensive as of June 17, 2020 and it highlights the science behind this drug and its potential implications to cardiovascular practice. 相似文献
12.
Kuganya Nirmalarajah Winfield Yim Patryk Aftanas Angel X. Li Altynay Shigayeva Lily Yip Zoe Zhong Allison J. McGeer Finlay Maguire Samira Mubareka Robert Kozak 《Influenza and other respiratory viruses》2023,17(9):e13179
Background
Remdesivir (RDV) has been shown to reduce hospitalization and mortality in COVID-19 patients. Resistance mutations caused by RDV are rare and have been predominantly reported in patients who are on prolonged therapy and immunocompromised. We investigate the effects of RDV treatment on intra-host SARS-CoV-2 diversity and low-frequency mutations in moderately ill hospitalized COVID-19 patients and compare them to patients without RDV treatment.Methods
From March 2020 to April 2022, sequential collections of nasopharyngeal and mid-turbinate swabs were obtained from 14 patients with and 30 patients without RDV treatment. Demographic and clinical data on all patients were reviewed. A total of 109 samples were sequenced and mutation analyses were performed.Results
Previously reported drug resistant mutations in nsp12 were not identified during short courses of RDV therapy. In genes encoding and surrounding the replication complex (nsp6-nsp14), low-frequency minority variants were detected in 7/14 (50%) and 18/30 (60%) patients with and without RDV treatment, respectively. We did not detect significant differences in within-host diversity and positive selection between the RDV-treated and untreated groups.Conclusions
Minimal intra-host variability and stochastic low-frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. The barrier to RDV resistance is high in patients with moderate disease. Patients undergoing short regimens of RDV therapy should continue to be monitored. 相似文献13.
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Malgorzata Mikulska Diletta Testi Chiara Russo Elisa Balletto Chiara Sepulcri Linda Bussini Chiara Dentone Federica Magne Sílvia Policarpo Caterina Campoli Filippo Miselli Alessandro Cilli Chiara Ghiggi Sara Aquino Carmen Di Grazia Maddalena Giannella Daniele Roberto Giacobbe Antonio Vena Anna Maria Raiola Francesca Bonifazi Pierluigi Zinzani Michele Cavo Roberto Lemoli Emanuele Angelucci Pierluigi Viale Matteo Bassetti Michele Bartoletti 《British journal of haematology》2023,201(4):628-639
Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n = 120, 37%; sotrovimab, n = 73) or antivirals (n = 208, 63%; nirmatrelvir/ritonavir, n = 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n = 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p < 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n = 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate. 相似文献
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Christina G. Rivera Supavit Chesdachai Evan W. Draper Richard F. Arndt Kristin C. Mara Maria Gonzalez Suarez Raymund R. Razonable 《Influenza and other respiratory viruses》2023,17(5):e13136
Introduction
During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined.Methods
Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals.Results
Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001).Conclusions
This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir. 相似文献17.
《Value in health》2022,25(5):761-769
ObjectivesCOVID-19 is associated with significant morbidity and mortality. This study aims to synthesize evidence to assess the cost-effectiveness of remdesivir (RDV) for the treatment of hospitalized patients with COVID-19 in England and Wales.MethodsA probabilistic cost-effectiveness analysis was conducted informed by 2 large trials and uses a partitioned survival approach to assess short- and long-term clinical consequences and costs associated with COVID-19 in a hypothetical cohort of hospitalized patients requiring supplemental oxygen at the start of treatment. Given that it is uncertain whether RDV reduces death, 2 analyses are presented, assuming RDV either reduces death or does not. Published sources were used for long-term clinical, quality of life, and cost parameters.ResultsUnder the assumption that RDV reduces death, the incremental cost-effectiveness ratio for RDV is estimated at £11 881 per quality-adjusted life-year gained compared with standard of care (SoC) (probabilistic incremental cost-effectiveness ratio £12 400). The probability for RDV to be cost-effective is 74% at a willingness-to-pay threshold of £20 000 per quality-adjusted life-year gained. RDV was no longer cost-effective when the hazard ratio for overall survival compared with SoC was >0·915.ConclusionsResults from this study suggest that using RDV for the treatment of hospitalized patients with COVID-19 is likely to represent a cost-effective use of National Health Service resources at current willingness-to-pay threshold in England and Wales, only if it prevents death. Results needs to be interpreted caution as vaccination was introduced and the SoC and evidence available have also evolved considerably since the analysis is conducted. 相似文献
18.
《Value in health》2022,25(5):744-750
ObjectivesThis study aimed to estimate the cost-effectiveness of remdesivir, the first novel therapeutic to receive Emergency Use Authorization for the treatment of hospitalized patients with COVID-19, and identify key drivers of value to guide future pricing and reimbursement efforts.MethodsA Markov model evaluated the cost-effectiveness of remdesivir in patients hospitalized with COVID-19 from a US healthcare sector perspective. A lifetime time horizon captured potential long-term costs and outcomes. Model outcomes included discounted total costs, life-years, and quality-adjusted life-years (QALYs). Remdesivir was modeled as an addition to standard of care and compared with standard of care alone, including dexamethasone for patients requiring respiratory support. COVID-19 hospitalizations were assumed to be reimbursed through a single payment based on the respiratory support received alongside a remdesivir carveout payment in the base case. Sensitivity and scenario analyses identified key drivers.ResultsAt a unit price of $520 per vial and assuming no survival benefit with remdesivir, the incremental cost-effectiveness was $298 200/QALY for patients with moderate to severe COVID-19 and $1 847 000/QALY for patients with mild COVID-19. Although current data do not support a survival benefit, if one was assumed, the cost-effectiveness estimate was $50 100/QALY for the moderate to severe population and $103 400/QALY for the mild population. Another key driver included the hospitalization payment structure (per diem vs bundled payment).ConclusionsWith the current evidence available, remdesivir’s price is too high to align with its expected health gains for hospitalized patients with COVID-19. Results from this study provide a rationale for iterative health technology assessment. 相似文献
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Florencia A. T. Boshier Juanita Pang Justin Penner Matthew Parker Nele Alders Alasdair Bamford Louis Grandjean Stephanie Grunewald James Hatcher Timothy Best Caroline Dalton Patricia Dyal Bynoe Claire Frauenfelder Jutta Keglmeier Phoebe Myerson Sunando Roy Rachel Williams Thushan I. de Silva Richard A. Goldstein Judith Breuer 《Journal of medical virology》2022,94(1):161-172
Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections. 相似文献
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Katharina S. Schmitz Mona V. Lange Lennert Gommers Kim Handrejk Danielle P. Porter Christopher A. Alabi Anne Moscona Matteo Porotto Rory D. de Vries Rik L. de Swart 《Viruses》2022,14(6)
Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks. 相似文献