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1.
Riv Psichiatr ; 56(1): 53-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33560276

RESUMO

Infection outbreak has been prevalent since previous decades. The impact of infection outbreak not merely limited to physical suffering but grounded for massive mental health issues. The fear of getting contagion and persistent exposure to diverse medication and vaccination contribute enormously to develop mental health issues among people. During previous infection treatment with diverse vaccination and antiviral agent, the common mental health issues found to be a mood disorder, delirium, schizophrenia, and psychotic symptoms. Cumbersomely, it is almost impossible to treat mental health issues during the pandemic with the help of only pharmacological availability. Hence psychological intervention is also important to ameliorate better consequences. The current study highlights the impact of CoViD-19 related diverse medication and vaccination on the mental health of the people.


Assuntos
Antivirais/efeitos adversos , Transtornos Mentais/induzido quimicamente , Saúde Mental , Pandemias , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/efeitos adversos , Alanina/análogos & derivados , Amidas/efeitos adversos , /efeitos adversos , Combinação de Medicamentos , Medo , Humanos , Lopinavir/efeitos adversos , Transtornos Mentais/psicologia , Oseltamivir/efeitos adversos , Pirazinas/efeitos adversos , Ribavirina/efeitos adversos , Ritonavir/efeitos adversos
2.
Eur Rev Med Pharmacol Sci ; 25(1): 541-548, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33506946

RESUMO

OBJECTIVE: List the clinical data of the role of remdesivir in COVID-19, and try to make an objective evaluation and analyze its feasibility. MATERIALS AND METHODS: The keywords of "remdesivir", "COVID-19" and "SARS-CoV-2" were systematically searched in PubMed and Web of Science. After removing the repetitions, we summarize articles, letters, and comments on remdesivir in the treatment of COVID-19. RESULTS: In this review, we summarize clinical case of using remdesivir in the treatment of COVID-19, analyzed the final treatment results, and judged whether the drug was effective for the treatment of COVID-19. Also, attention was paid to the side effects of the drug. CONCLUSIONS: According to the clinical results, it was found that remdesivir was effective in the treatment of COVID-19. The drug has side effects, but the symptoms were mild and disappeared immediately after discontinuation of medication.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , /tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Humanos , Resultado do Tratamento
3.
PLoS Med ; 17(12): e1003501, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33378357

RESUMO

BACKGROUND: Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. METHODS AND FINDINGS: We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527). CONCLUSIONS: In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hidroxicloroquina/efeitos adversos , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/análogos & derivados , Alanina/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , /terapia , Estado Terminal , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Metanálise em Rede , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Medwave ; 20(11)31-12-2020.
Artigo em Inglês | LILACS | ID: biblio-1146025

RESUMO

OBJETIVO: Esta revisión sistemática viva tiene como objetivo entregar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre los efectos de remdesivir en pacientes con COVID-19. MÉTODOS: Se buscaron ensayos aleatorios que evaluaran el uso de remdesivir versus placebo o ningún tratamiento en pacientes con COVID-19. Se realizó una búsqueda en la plataforma L·OVE COVID-19 (Living OVerview of Evidence), un sistema que mantiene búsquedas regulares en bases de datos, registros de ensayos, servidores preprint y sitios web relevantes en COVID-19. Todas las búsquedas fueron realizadas hasta el 25 de agosto de 2020. No se aplicaron restricciones de fecha ni de idioma. Dos revisores evaluaron de forma independiente los artículos potencialmente elegibles, de acuerdo con criterios de selección predefinidos, y extrajeron los datos mediante un formulario estandarizado. Los resultados fueron combinados mediante un metanálisis utilizando modelos de efectos aleatorios y evaluamos la certeza de la evidencia utilizando el método GRADE. Una versión viva de esta revisión estará abiertamente disponible durante la pandemia de COVID-19. RESULTADOS: La búsqueda inicial arrojó 574 referencias. Finalmente, identificamos 3 ensayos aleatorios, que evaluaban el uso de remdesivir adicionado al tratamiento estándar versus tratamiento estándar. La evidencia es muy incierta acerca del efecto del remdesivir sobre la mortalidad (RR 0,7; IC del 95%: 0,46 a 1,05; certeza de la evidencia muy baja) y la necesidad de ventilación mecánica invasiva (RR 0,69; IC del 95%: 0,39 a 1,24; certeza de evidencia muy baja). Por otro lado, es probable que el uso de remdesivir produzca un aumento en la incidencia de efectos adversos en pacientes con COVID-19 (RR 1,29; IC del 95%: 0,58 a 2,84; evidencia de certeza moderada). CONCLUSIONES: La evidencia disponible sobre el papel del remdesivir en el tratamiento de pacientes con COVID-19 es insuficiente en relación a los desenlaces críticos para tomar decisiones, por lo que no es posible realizar un correcto balance entre los beneficios potenciales, los efectos adversos y los costos.


OBJECTIVE: Provide a timely, rigorous and continuously updated summary of the evidence on the role of remdesivir in the treatment of patients with COVID-19. METHODS: Eligible studies were randomized trials evaluating the effect of remdesivir versus placebo or no treatment. We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in databases, trial registries, preprint servers and websites relevant to COVID-19. All the searches covered the period until 25 August 2020. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned, standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. RESULTS: Our search strategy yielded 574 references. Finally, we included three randomized trials evaluating remdesivir in addition to standard care versus standard care alone. The evidence is very uncertain about the effect of remdesivir on mortality (RR 0.7, 95% CI 0.46 to 1.05; very low certainty evidence) and the need for invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24; very low certainty evidence). On the other hand, remdesivir likely results in a large increase in the incidence of adverse effects in patients with COVID-19 (RR 1.29, 95% CI 0.58 to 2.84; moderate certainty evidence). CONCLUSIONS: The evidence is insufficient for the outcomes critical for making decisions on the role of remdesivir in the treatment of patients with COVID-19, so it is impossible to balance potential benefits, if there are any, with the adverse effects and costs.


Assuntos
Humanos , Antivirais/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Infecções por Coronavirus/tratamento farmacológico , Alanina/análogos & derivados , Antivirais/efeitos adversos , Pneumonia Viral/mortalidade , Respiração Artificial/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Resultado do Tratamento , Infecções por Coronavirus/mortalidade , Alanina/efeitos adversos , Alanina/uso terapêutico
5.
Trials ; 21(1): 1028, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353566

RESUMO

BACKGROUND: Randomised controlled trials (RCTs) provide valuable information and inform the development of harm profiles of new treatments. Harms are typically assessed through the collection of adverse events (AEs). Despite AEs being routine outcomes collected in trials, analysis and reporting of AEs in journal articles are continually shown to be suboptimal. One key challenge is the large volume of AEs, which can make evaluation and communication problematic. Prominent practice is to report frequency tables of AEs by arm. Visual displays offer an effective solution to assess and communicate complex information; however, they are rarely used and there is a lack of practical guidance on what and how to visually display complex AE data. METHODS: In this article, we demonstrate the use of two plots identified to be beneficial for wide use in RCTs, since both can display multiple AEs and are suitable to display point estimates for binary, count, or time-to-event AE data: the volcano and dot plots. We compare and contrast the use of data visualisations against traditional frequency table reporting, using published AE information in two placebo-controlled trials, of remdesivir for COVID-19 and GDNF for Parkinson disease. We introduce statistical programmes for implementation in Stata. RESULTS/CASE STUDY: Visualisations of AEs in the COVID-19 trial communicated a risk profile for remdesivir which differed from the main message in the published authors' conclusion. In the Parkinson's disease trial of GDNF, the visualisation provided immediate communication of harm signals, which had otherwise been contained within lengthy descriptive text and tables. Asymmetry in the volcano plot helped flag extreme events that were less obvious from review of the frequency table and dot plot. The dot plot allowed a more comprehensive representation by means of a more detailed summary. CONCLUSIONS: Visualisations can better support investigators to assimilate large volumes of data and enable improved informal between-arm comparisons compared to tables. We endorse increased uptake for use in trial publications. Care in construction of visual displays needs to be taken as there can be potential to overemphasise treatment effects in some circumstances.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Apresentação de Dados , Visualização de Dados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Projetos de Pesquisa/normas , Monofosfato de Adenosina/efeitos adversos , Alanina/efeitos adversos , Antiparkinsonianos/efeitos adversos , Antivirais/efeitos adversos , Gráficos por Computador , Confiabilidade dos Dados , Análise de Dados , Monitoramento de Medicamentos/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Medwave ; 20(11): e8080, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33361753

RESUMO

Objective: Provide a timely, rigorous and continuously updated summary of the evidence on the role of remdesivir in the treatment of patients with COVID-19. Methods: Eligible studies were randomized trials evaluating the effect of remdesivir versus placebo or no treatment. We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in databases, trial registries, preprint servers and websites relevant to COVID-19. All the searches covered the period until 25 August 2020. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned, standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. Results: Our search strategy yielded 574 references. Finally, we included three randomized trials evaluating remdesivir in addition to standard care versus standard care alone. The evidence is very uncertain about the effect of remdesivir on mortality (RR 0.7, 95% CI 0.46 to 1.05; very low certainty evidence) and the need for invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24; very low certainty evidence). On the other hand, remdesivir likely results in a large increase in the incidence of adverse effects in patients with COVID-19 (RR 1.29, 95% CI 0.58 to 2.84; moderate certainty evidence). Conclusions: The evidence is insufficient for the outcomes critical for making decisions on the role of remdesivir in the treatment of patients with COVID-19, so it is impossible to balance potential benefits, if there are any, with the adverse effects and costs. PROSPERO registration number: CRD42020183384.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , /tratamento farmacológico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos , Resultado do Tratamento
7.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
8.
Eur Rev Med Pharmacol Sci ; 24(18): 9739-9743, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33015819

RESUMO

OBJECTIVE: Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA polymerases. It has been recognized recently as a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV5). We aimed at determining which drugs used in dentistry interact with Remdesivir in order to avoid adverse reactions that may worsen the condition of patients with COVID-19. MATERIALS AND METHODS: A literature review was conducted to identify potential drug interactions between remdesivir (used in the treatment of COVID-19) and drugs prescribed in dentistry. The search was made in the databases PubMed and MEDLINE and official websites using key terms remdesivir, drug interactions and dentistry for articles published up to 31st July 2020. RESULTS: According to the articles reviewed, a total of 279 drugs interact with Remdesivir. Two major interactions have been reported, 277 moderate drug interactions, and one with alcohol/food. The drug interactions involving drugs prescribed in dentistry are all moderate drug interactions and are (according to drug group): (1) antibiotics: azithromycin, clavulanate, doxycycline, erythromycin, levofloxacin; (2) antifungals: clotrimazole, fluconazole, itraconazole, ketoconazole; (3) non-steroidal anti-inflammatories (NAIDS): celecoxib diclofenac, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, mefenamic acid, naproxen, piroxicam. CONCLUSIONS: It is clinically necessary for oral health professionals to be aware of possible drug interactions that may occur between remdesivir and drugs commonly prescribed in dentistry in order to prevent adverse reactions that may even endanger the life of a patient with COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus , Odontologia , Interações Medicamentosas , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pneumonia Viral/tratamento farmacológico
9.
Clin Med (Lond) ; 20(6): e215-e217, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32863273

RESUMO

The emergence of the novel beta coronavirus SARS-CoV-2 and the ensuing COVID-19 pandemic has generated a rapidly evolving research landscape in the search for new therapeutic agents. The intravenous antiviral drug remdesivir has in vitro activity against SARS-CoV-2 and now studies have reported its clinical efficacy, demonstrating shorter time to recovery in hospitalised patients with severe COVID-19. Adverse event rates were low and remdesivir has now received conditional marketing authorisation from the European Medicines Agency. An interim clinical commissioning policy is in place in the UK. These studies make remdesivir the first antiviral drug able to alter the natural history of severe COVID-19, and a benchmark for the comparison of new therapies in the future. Ongoing studies are investigating its use in early mild/moderate COVID-19, alternative formulations, and the combination of remdesivir with immunomodulatory agents.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Administração Intravenosa , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Antimicrob Agents Chemother ; 64(11)2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32868327

RESUMO

Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether ß-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/terapia , Furanos/urina , Pneumonia Viral/terapia , Pirróis/urina , Triazinas/urina , beta-Ciclodextrinas/urina , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/química , Alanina/metabolismo , Antivirais/efeitos adversos , Antivirais/química , Antivirais/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/cirurgia , Infecções por Coronavirus/virologia , Interações Medicamentosas , Furanos/efeitos adversos , Furanos/química , Humanos , Unidades de Terapia Intensiva , Transplante de Pulmão , Insuficiência de Múltiplos Órgãos , Pandemias , Pneumonia Viral/cirurgia , Pneumonia Viral/virologia , Pirróis/efeitos adversos , Pirróis/química , Diálise Renal , Transplantados , Triazinas/efeitos adversos , Triazinas/química , beta-Ciclodextrinas/efeitos adversos , beta-Ciclodextrinas/química
11.
Expert Opin Investig Drugs ; 29(11): 1195-1198, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32896184

RESUMO

INTRODUCTION: In clinical trial for the Ebola virus, the broad-spectrum anti-viral agent remdesivir was shown to have a good safety profile. Remdesivir is now being tested in severe COVID-19. AREAS COVERED: The Gilead Sciences SIMPLE trial suggests that the short-term use of remdesivir probably does not increase mortality dramatically or have serious short-term toxicity when used to treat severe COVID-19. The Adaptive COVID-19 treatment trials (ACTT1) trial showed that remdesivir may shorten recovery and decrease mortality in severe COVID-19 without increasing adverse effects. EXPERT OPINION: It seems to me that we have learnt very little from the SIMPLE trial, and this would be predicted from a trial that has no control or placebo group. The results of ACTT1 were reported early after an interim analysis showed that a higher than expected number of recoveries had occurred. There was an indication that remdesivir may be reducing mortality, but this was no statistical significance. The trial is continuing, and the final data are eagerly awaited to determine whether remdesivir is a game-changing remedy or a ripple in the ongoing search for a medicine for the treatment of COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Ther Innov Regul Sci ; 54(5): 1236-1255, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32865809

RESUMO

Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/tratamento farmacológico , Confiabilidade dos Dados , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , China , Comitês de Monitoramento de Dados de Ensaios Clínicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Tempo , Resultado do Tratamento
13.
Emerg Med J ; 37(8): 522-523, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32753375

RESUMO

A short-cut review of the available medical literature was carried out to establish whether remdesivir was an effective treatment for patients with confirmed COVID-19 infection. After abstract review, five papers were found to answer this clinical question using the detailed search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that despite some recent promising studies, further well-designed and larger trials are needed to answer this specific question.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Adulto , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Resultado do Tratamento
14.
JAMA ; 324(11): 1048-1057, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32821939

RESUMO

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Administração Intravenosa , Idoso , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Infecções por Coronavirus/mortalidade , Esquema de Medicação , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Gravidade do Paciente , Pneumonia Viral/mortalidade , Resultado do Tratamento
15.
Hepatol Int ; 14(5): 881-883, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32725454
16.
Gastroenterol Hepatol ; 43(8): 472-480, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32727662

RESUMO

The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganization of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Hepatopatias/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Fatores Etários , Alanina/efeitos adversos , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Ductos Biliares/virologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Crônica , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Suscetibilidade a Doenças , Gastroenterologia/organização & administração , Recursos em Saúde/provisão & distribução , Hepatite Crônica/tratamento farmacológico , Hepatite Crônica/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Testes de Função Hepática , Transplante de Fígado , Obesidade/epidemiologia , Alocação de Recursos , Fatores de Risco
17.
Clin Gastroenterol Hepatol ; 18(12): 2835-2836, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32721580

RESUMO

Remdesivir is a nucleotide analog prodrug with antiviral activity against a broad spectrum of human coronavirus in cell cultures and mouse models including severe acute respiratory syndrome-associated coronavirus 2. Recently, the Food and Drug Agency (FDA) and the European Medicines Agency (EMA) recommended remdesivir for the treatment of patients hospitalized with severe coronavirus disease 2019 (COVID-19) infection.1,2 In the remdesivir clinical development program, some cases have raised concerns regarding potential hepatobiliary disorders associated with remdesivir, including in healthy volunteers and patients with COVID-19.3 In cohort studies of patients hospitalized for severe COVID-19 who were treated with compassionate-use remdesivir, elevated hepatic enzymes were the most frequent adverse drug reaction reported.4,5 In the first randomized, double-blind, placebo-controlled clinical trial assessing the effect of intravenous remdesivir in adults admitted to hospital with severe COVID-19 (n = 237), a higher proportion of remdesivir recipients than placebo recipients had dosing prematurely stopped by the investigators because of adverse events including aminotransferase or bilirubin increases (3 versus 0).6 Although there is no signal from the available data of severe hepatotoxicity or drug-induced liver injury in clinical trials, the number of patients exposed to remdesivir was too limited. Therefore, there is an urgent need to investigate the hepatic safety profile associated with remdesivir in COVID-19 patients.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por Coronavirus/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia
18.
Int J Infect Dis ; 98: 290-293, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32619764

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the virus responsible for the coronavirus disease 2019 (COVID-19) outbreak worldwide. Data on treatment are scare and parallels have been made between SARS-CoV-2 and other coronaviruses. Remdesivir is a broad-spectrum antiviral with efficient in vitro activity against SARS-CoV-2. Evidence of clinical improvement in patients with severe COVID-19 treated with remdesivir is controversial. The aim of this study was to describe the clinical outcomes and virological monitoring of the first five COVID-19 patients admitted to the intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France, for severe pneumonia related to SARS-CoV-2 and treated with remdesivir. Quantitative reverse transcription PCR was used to monitor SARS-CoV-2 in blood plasma and the lower and upper respiratory tract. Among the five patients treated, two needed mechanical ventilation and one needed high-flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load in the upper respiratory tract was observed in most cases, but two patients died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted before the initialy planned duration in four patients, two because of alanine aminotransferase elevations (3 to 5 normal range) and two because of renal failure requiring renal replacement. This case series of five COVID-19 patients requiring intensive care unit treatment for respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Feminino , França , Hospitalização , Humanos , Masculino , Pandemias , Pneumonia Viral/virologia , Carga Viral/efeitos dos fármacos , Suspensão de Tratamento
19.
J Allergy Clin Immunol ; 146(4): 786-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32710973

Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Hipersensibilidade a Drogas/etiologia , Fatores Imunológicos/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Amidas/administração & dosagem , Amidas/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Indóis/administração & dosagem , Indóis/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Índice de Gravidade de Doença
20.
Dtsch Med Wochenschr ; 145(15): 1063-1067, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32731280

RESUMO

The SARS-CoV-2 pandemic has rapidly spread around the world and has led to a substantial morbidity and mortality in many countries. Although Corona Virus Disease 19 (COVID-19) is primarily a respiratory tract infection, there is growing evidence that other organs including the cardiovascular system are affected by COVID-19. In this review, we summarize the association of myocardial injury with in-hospital mortality of COVID-19 patients. Furthermore, we discuss potential mechanisms of myocardial injury including myocarditis and vascular thrombosis. Last, we review the current evidence on drugs which have been evaluated or are currently tested for the treatment of COVID-19 patients.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Arterite , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Trombose Venosa
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