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1.
Pharmacol Res Perspect ; 9(1): e00705, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421347

RESUMO

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.


Assuntos
Antivirais/uso terapêutico , /tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Cloroquina/uso terapêutico , Interações Medicamentosas , Humanos , Lopinavir/uso terapêutico , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
2.
Adv Chronic Kidney Dis ; 27(5): 434-441, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33308510

RESUMO

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Insuficiência Renal Crônica/metabolismo , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , /prevenção & controle , /uso terapêutico , Cloroquina/uso terapêutico , Creatinina/metabolismo , Citidina/análogos & derivados , Citidina/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Hidroxicloroquina/uso terapêutico , Hidroxilaminas/uso terapêutico , Imunização Passiva , Interferons/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Eliminação Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
3.
Trials ; 21(1): 999, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276811

RESUMO

OBJECTIVES: A severe epidemic of COVID-19 has broken out in China and has become a major global public health event. We focus on the Acute Respiratory Distress Syndrome (ARDS)-like changes and overactivation of Th17 cells (these produce cytokines) in patients with COVID-19. We aim to explore the safety and efficacy of ixekizumab (an injectable drug for the treatment of autoimmune diseases) to prevent organ injury caused by the immune response to COVID-19. Ixekizumab is a human monoclonal antibody that binds to interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. TRIAL DESIGN: The experiment is divided into two stages. In the first stage, the open trial, 3 patients with COVID-19 are treated with ixekizumab, and the safety and efficacy are observed for 7 days. In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. This is a two-center, open-label, randomized controlled pilot trial with 2-arm parallel group design (1:1 ratio). PARTICIPANTS: Patients with COVID-19 aged 18-75 with increased Interleukin (IL)-6 levels will be enrolled, but patients with severe infections requiring intensive care will be excluded. The trial will be undertaken in two centers. The first stage is carried out in Xiangya Hospital of Central South University, and the second stage is carried out simultaneously in the Third Xiangya Hospital of Central South University. INTERVENTION AND COMPARATOR: In the first stage, three subjects are given ixekizumab ("Taltz") (80 mg/ml, 160 mg as a single hypodermic injection) and antiviral therapy (α-interferon (administer 5 million U by aerosol inhalation twice daily), lopinavir/ritonavir (administer 100mg by mouth twice daily, for the course of therapy no more than 10 days), chloroquine (administer 500mg by mouth twice daily, for the course of therapy no more than 10 days), ribavirin (administer 500mg by intravenous injection two to three times a day, for the course of therapy no more than 10 days), or arbidol (administer 200mg by mouth three times a day, for the course of therapy no more than 10 days), but not more than 3 types). The treatment course of the first stage is 7 days. In the second stage, 40 randomized patients will receive the following treatments--Group 1: ixekizumab (80 mg/ml, 160 mg as a single hypodermic injection) with antiviral therapy (the same scheme as in the first stage); Group 2: antiviral therapy alone (the same scheme as in the first stage). The length of the second treatment course is 14 days. MAIN OUTCOMES: The primary outcome is a change in pulmonary CT severity score (an imaging tool for assessing COVID-19, which scores on the basis of all abnormal areas involved). Pulmonary CT severity score is assessed on the 7th day, 14th day, or at discharge. RANDOMISATION: In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. The eLite random system of Nanjing Medical University is used for randomization. BLINDING (MASKING): The main efficacy indicator, the CT results, will be evaluated by the third-party blinded and independent research team. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. TRIAL STATUS: Trial registration number is ChiCTR2000030703 (version 1.7 as of March 19, 2020). The recruitment is ongoing, and the date recruitment was initiated in June 2020. The anticipated date of the end of data collection is June 2021. TRIAL REGISTRATION: The name of the trial register is the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000030703 ( http://www.chictr.org.cn/ ). The date of trial registration is 10 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , /efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , /prevenção & controle , Estudos de Casos e Controles , China/epidemiologia , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Quimioterapia Combinada , Humanos , Indóis/administração & dosagem , Indóis/uso terapêutico , Interleucina-17/imunologia , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Segurança , Células Th17/imunologia , Resultado do Tratamento
4.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33305558

RESUMO

The index case of COVID-19 in Sabzevar, Khorasan Razavi Province in northeastern Iran, was an 80-year-old man with a history of psycho-neurological illness and acute respiratory clinical symptoms, and a history of travel to areas with confirmed COVID-19 cases in Gorgan City. He was identified on February 16, 2020, and his laboratory diagnosis was made on February 26, 2020. The patient was hospitalized and discharged after complete recovery. The contacts of the patient were traced, revealing the infection of his 30-year-old son with milder symptoms of COVID-19, which was confirmed through a laboratory test on April 4, 2020 and was recommended for home quarantine. Other family members had no signs of COVID-19.


Assuntos
/diagnóstico , /genética , Adulto , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , /virologia , Busca de Comunicante/métodos , Quimioterapia Combinada , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Quarentena/métodos , /virologia , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Doença Relacionada a Viagens , Resultado do Tratamento , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico
5.
Eur Rev Med Pharmacol Sci ; 24(22): 11977-11981, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275275

RESUMO

Researchers have found many similarities between the 2003 severe acute respiratory syndrome (SARS) virus and SARS-CoV-19 through existing data that reveal the SARS's cause. Artificial intelligence (AI) learning models can be created to predict drug structures that can be used to treat COVID-19. Despite the effectively demonstrated repurposed drugs, more repurposed drugs should be recognized. Furthermore, technological advancements have been helpful in the battle against COVID-19. Machine intelligence technology can support this procedure by rapidly determining adequate and effective drugs against COVID-19 and by overcoming any barrier between a large number of repurposed drugs, laboratory/clinical testing, and final drug authorization. This paper reviews the proposed vaccines and medicines for SARS-CoV-2 and the current application of AI in drug repurposing for COVID-19 treatment.


Assuntos
Inteligência Artificial , Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Ácido Ascórbico/uso terapêutico , /uso terapêutico , Cloroquina/uso terapêutico , Aprendizado Profundo , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Lopinavir/uso terapêutico , Aprendizado de Máquina , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Vitaminas/uso terapêutico
6.
BMC Infect Dis ; 20(1): 929, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276734

RESUMO

BACKGROUND: Treatment of chronic hepatitis C virus infection with direct acting antiviral therapy results in viral elimination in over 90% of cases. The duration of treatment required to achieve cure differs between individuals and relapse can occur. We asked whether cellular and transcriptional profiling of peripheral blood collected during treatment could identify biomarkers predictive of treatment outcome. METHODS: We analyzed peripheral blood collected during treatment of genotype 1 HCV with 24 weeks of sofosbuvir and weight-based or low dose ribavirin in a trial in which 29% of patients relapsed. Changes in host immunity during treatment were assessed by flow cytometry and whole blood gene expression profiling. Differences in expression of immune-relevant transcripts based on treatment outcome were analyzed using the Nanostring Human Immunology V2 panel. RESULTS: Multiple cellular populations changed during treatment, but pre-treatment neutrophil counts were lower and natural post-treatment killer cell counts were higher in patients who relapsed. Pre-treatment expression of genes associated with interferon-signaling, T-cell dysfunction, and T-cell co-stimulation differed by treatment outcome. We identified a pre- and post-treatment gene expression signature with high predictive capacity for distinguishing treatment outcome, but neither signature was sufficiently robust to suggest viability for clinical use. CONCLUSIONS: Patients who relapse after hepatitis C virus therapy differ immunologically from non-relapsers based on expression of transcripts related to interferon signaling and T-cell dysfunction, as well as by peripheral neutrophil and NK-cell concentrations. These data provide insight into the host immunologic basis of relapse after DAA therapy for HCV and suggests mechanisms which may be relevant for understanding outcomes with currently approved regimens.


Assuntos
Antivirais/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Quimioterapia Combinada , Feminino , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Interferons/metabolismo , Células Matadoras Naturais/imunologia , Estudos Longitudinais , Masculino , Neutrófilos/imunologia , Recidiva , Linfócitos T/imunologia , Transcriptoma , Resultado do Tratamento
9.
Med J Malaysia ; 75(6): 710-716, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33219182

RESUMO

INTRODUCTION: Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate clinical events, up to 5-10% may have severe, life threatening events that urgently require effective drugs. The purpose of this systematic review is to evaluate the effectiveness of antiviral therapies in the treatment of COVID-19. METHODS: An extensive search was performed in PubMed, EMBASE, Cochrane Library for randomised controlled trials (RCTs), prospective case series studies that evaluated therapies COVID-19. The outcomes searched for were mortality, recovery rate, length of hospital stay and clinical improvement from January to May 15, 2020. Independent reviewers searched, identified, screened, and related studies were included. RESULTS: Total of five RCTs on 439 patients and seventeen case series involving 1656 patients were found in the specified review period that reported the use of Lopinavir, Ritonavir, Remdesivir. Oseltamivir, Ribavirin in patients with COVID-19; but none of which showed efficacy of antiviral therapy. Such current findings impede researchers from recommending an appropriate and effective antiviral therapy against COVID-19, making it a serious concern for the global community. DISCUSSION: In the present pandemic and any future epidemics, all the related authorities should pursue many more RCTs, cohort and case series for a prospective outcome in the management and treatment guidelines.


Assuntos
/tratamento farmacológico , Pandemias , Ribavirina/uso terapêutico , Antivirais/uso terapêutico , Humanos
10.
Arq Gastroenterol ; 57(3): 267-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027477

RESUMO

BACKGROUND: Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients' IR profile while using such therapies. OBJECTIVE: - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS: We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients' levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS: We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION: In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).


Assuntos
Hepatite C Crônica , Resistência à Insulina , Antivirais/farmacologia , Antivirais/uso terapêutico , Brasil , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Resultado do Tratamento
11.
Am J Emerg Med ; 38(11): 2405-2415, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33041111

RESUMO

INTRODUCTION: There is a pressing need for COVID-19 transmission control and effective treatments. We aim to evaluate the safety and effectiveness of SARS-CoV-2 pharmacologic therapies as of August 2, 2020 according to study level of evidence. METHODS: PubMed, ScienceDirect, Cochrane Library, JAMA Network and PNAS were searched. The following keywords were used: ((COVID-19) OR (SARS-CoV-2)) AND ((((((therapeutics) OR (treatment)) OR (vaccine)) OR (hydroxychloroquine)) OR (antiviral)) OR (prognosis)). Results included peer-reviewed studies published in English. RESULTS: 15 peer-reviewed articles met study inclusion criteria, of which 14 were RCTs and one was a systematic review with meta-analysis. The following pharmacologic therapies were evaluated: chloroquine (CQ), hydroxychloroquine (HCQ), antivirals therapies, plasma therapy, anti-inflammatories, and a vaccine. CONCLUSION: According to level 1 evidence reviewed here, the most effective SARS-Co-V-2 pharmacologic treatments include remdesivir for mild to severe disease, and a triple regimen therapy consisting of lopinavir-ritonavir, ribavirin and interferon beta-1b for mild to moderate disease. Also, dexamethasone significantly reduced mortality in those requiring respiratory support. However, there is still a great need for detailed level 1 evidence on pharmacologic therapies.


Assuntos
/tratamento farmacológico , /prevenção & controle , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Medicina Baseada em Evidências , Humanos , Hidroxicloroquina/uso terapêutico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Revisões Sistemáticas como Assunto
12.
Medicine (Baltimore) ; 99(42): e21972, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080669

RESUMO

Treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease was difficult in the past because of the use of interferon (IFN). It was associated with high risk IFN-related adverse reactions due to reduced renal clearance of IFN. This study aimed to evaluate the antiviral efficacy, safety, and tolerability of ombitasvir/paritaprevir/ritonavir/ribavirin in chronic kidney disease patients infected with chronic HCV.This observational, open-label prospective study was carried out on 103 patients infected chronic HCV with different grades of renal impairment. Paritaprevir/ritonavir and ombitasvir (75/50/12.5 mg) twice daily plus ribavirin were given to the patients for 12 weeks. Dose adjustment of ribavirin was done according to degree of renal impairment.Sustained virological response (12 weeks after the end of treatment) occurred in 101 patients (98.1%). Anemia occurred in 48 patients. No serious adverse events were observed in any patient.Paritaprevir/ritonavir and ombitasvir plus ribavirin for 12 weeks was considered to be safe and effective in the treatment of chronic HCV infected patients with varying degrees of renal impairment.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Falência Renal Crônica/complicações , Adulto , Idoso , Anilidas/uso terapêutico , Carbamatos/uso terapêutico , Quimioterapia Combinada , Egito , Feminino , Humanos , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Resposta Viral Sustentada
13.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 831-837, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105927

RESUMO

Objective: To understand the effectiveness and safety sofosbuvir/velpatasvir (SOF/VEL) combination ±ribavirin in the treatment of chronic hepatitis C virus (HCV) infection in China. Methods: A total of 96 Chinese adults with chronic HCV infection who were treated with SOF/VEL combination ± ribavirin for 12 weeks between July 2018 and February 2020 were selected. HCV RNA, routine blood test, liver, kidney and coagulation function, abdominal Color Doppler ultrasound or CT and liver stiffness were detected at baseline, 4 weeks of treatment, end of treatment and 12 weeks of follow-up. Adverse events and laboratory abnormalities during the treatment were recorded. A t-test was used to compare the measurement data between the two groups, and the analysis of variance was used for multiple group comparison. Results: A total of 93 cases (96.9%) achieved sustained virological response (SVR12), of which 3 cases had relapsed. 88 cases (91.7%, 88/96) had achieved rapid virological response (RVR). 96 cases (100%) had achieved virological response by the end of treatment (EOT). In patients with decompensated liver cirrhosis, the average baseline Child-Pugh score and Model for End-Stage Liver Disease score was 7.4±1.0, and 11.4±1.7, respectively. Among them, 12 cases of the SOF/VEL combined with RBV treatment had achieved SVR12 (100%) at 12 weeks, while only 3 of the 5 cases of single-tablet regimen of SOF/VEL had achieved SVR12 (60%). There was no significant difference between creatinine levels and baseline during or 12 weeks after treatment. The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 6.3% (5/79), while that in patients with decompensated cirrhosis was 35.3% (6/17). The most common adverse events were hyperbilirubinemia, fatigue and anemia. There were no serious adverse events, deaths or discontinuation of treatment due to adverse events. Conclusion: SOF/VEL combination ± ribavirin in the treatment of various common genotypes of chronic hepatitis C, compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma has higher SVR12 in China, and the tolerance and safety are good.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C Crônica , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , China , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Cirrose Hepática/virologia , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do Tratamento
14.
PLoS One ; 15(10): e0236543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33006987

RESUMO

OBJECTIVES: Recently, the results of two economic evaluations were published both of which seemingly demonstrate the cost-effectiveness of sofosbuvir-based regimens for the treatment of chronic hepatitis C genotype 1 infection in Germany. Both analyses were sponsored by the manufacturer of sofosbuvir and use a different methodology: Whereas one evaluation is based on a conventional cost-utility analysis, the other rests upon the efficiency-frontier method used by the German Institute for Quality and Efficiency in Health Care (IQWiG). The purpose of this study is to reanalysis the results of both economic evaluations in combination. DESIGN: Reanalysis of published decision modelling results. SETTING: Primary care in Germany. PARTICIPANTS: Patients with chronic hepatitis C genotype 1 infection (treatment-naïve and -experienced, cirrhotic and non-cirrhotic). INTERVENTIONS: Sofosbuvir, other anti-hepatitis C virus drugs, and no treatment. PRIMARY AND SECONDARY OUTCOME MEASURES: Cost per unit of health benefit and cost per quality-adjusted life year. RESULTS: Reanalysis of the results of both economic evaluations in combination reveals an unclear rationale for choosing the selected cost-effectiveness methods as well as a potential publication bias, favoring the product of the manufacturer. Based on the reanalysis, sofosbuvir is not cost-effective in treatment-experienced non-cirrhotic patients, potentially lacks cost-effectiveness in treatment-experienced cirrhotic patients, and is only partially cost-effective in treatment-naïve non-cirrhotic patients. Taken together, these results indicate a lack of cost-effectiveness in three quarters of the German patient population. CONCLUSIONS: Two economic evaluations on sofosbuvir suggest, in combination, that sofosbuvir cannot be considered a cost-effective treatment in three quarters of the German patient population.


Assuntos
Antivirais/economia , Hepacivirus/genética , Hepatite C Crônica/economia , Sofosbuvir/economia , Antivirais/uso terapêutico , Quimioterapia Combinada , Genótipo , Alemanha/epidemiologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Ribavirina/economia , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico
15.
Trials ; 21(1): 866, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081849

RESUMO

OBJECTIVES: 1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. PARTICIPANTS: The trial will be undertaken in a tertiary care center of the country where both Covid and non-Covid patients are getting treated. All patients who are confirmed positive and admitted will be screened for the eligibility criteria and will be enrolled in the study after a written informed consent. Patients will be categorised as non-severe or severe based on predefined criteria. INCLUSION CRITERIA (ALL REQUIRED): 1. Age ≥18 years at time of participation in the study 2. Laboratory (RT-PCR) confirmed infection with SARS-CoV-2 3. Symptomatic (severe or non-severe) Covid-19 disease 4. Willingness of study participant to accept randomization to any assigned treatment arm EXCLUSION CRITERIA: 1. Use of medications that are contraindicated with Lopinavir/Ritonavir, Hydroxychloroquine/Chloroquine, or Ribavirin and that cannot be replaced or stopped 2. Patient already on antiretroviral therapy with Lopinavir-Ritonavir based regimen or on Hydroxychloroquine/Chloroquine or on Ribavirin 3. Any known contraindication to test drugs such as retinopathy and QT prolongation 4. Known allergic reaction or inability to take orally of Lopinavir-ritonavir, Hydroxychloroquine/ Chloroquine, Ribavarin 5. Pregnant or breastfeeding females 6. Receipt of any experimental treatment for 2019-nCoV (off-label, compassionate use, or trial related) within 30 days prior to participation in the present study or want to participate after enrolment INTERVENTION AND COMPARATOR: Two therapeutic interventions for non-severe category and three for severe category as described below NON-SEVERE TREATMENT ARMS (NS-GROUP): Treatment Arm Drug A Standard Treatment (STNS) B Hydroxychloroquine 400 mg twice on first day followed by 400 mg per oral daily for 10 days + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STNS) Standard Treatment for non-severe cases (STNS): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Hydration, Proper Nutrition, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. SEVERE GROUP TREATMENT ARMS (S-GROUP): Treatment Arm Drug A Standard Treatment (STs) B Hydroxychloroquine 400mg BD on day1 followed by 400 mg once daily + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs) C Lopinavir(200mg) + Ritonavir (50mg) two tablets twice daily+ Ribavirin (1.2g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs)6 Standard Treatment for severe patients (STs): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Fluid Therapy, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Oxygen supplementation (As required), Invasive ventilation (As required), Antibiotic agents for other associated infections (according to 2019 ATS/IDSA guidelines for non-ICU and ICU patients), Vasopressor support, Renal-replacement therapy, Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. MAIN OUTCOMES: Primary endpoints: (1) Time to Clinical recovery (TTCR) defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, oxygen saturation, and alleviation of cough, sustained for at least 72 hours. (2) Time to SARS-CoV-2 RT-PCR negative in upper respiratory tract specimen, time to laboratory recovery of each organ involvement. Secondary Endpoints: All causes mortality, Frequency of respiratory progression (defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support), time to defervescence (in those with fever at enrolment), frequency of requirement for supplemental oxygen or non-invasive ventilation, frequency of requirement for mechanical ventilation, frequency of serious adverse events as per DAIDS table grade of severity. Outcomes are monitored for 28 days from the time of enrolment into the study OR until the patient is discharged or death whichever is longer. RANDOMIZATION: The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. BLINDING (MASKING): This is an open labelled study i.e. Study assigned treatment will be known to the research team, the investigators and participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Since it is an exploratory trial as COVID-19 being a new disease, all patients who came under the purview of the inclusion criteria within the study period (5 months duration of the recruitment period of the total 6 months duration of the study i.e. from the month of June, 2020 to October 2020) and who have consented for the study will be included. TRIAL STATUS: Protocol version:1.0 Recruitment start: June 3rd, 2020 (Ongoing) Recruitment finish (expected): October 31st, 2020 TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI): CTRI/2020/06/025575 . Registration on 03 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Ribavirina/uso terapêutico , Administração Oral , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Antivirais/administração & dosagem , Betacoronavirus/genética , Protocolos Clínicos , Terapia Combinada , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Índia/epidemiologia , Consentimento Livre e Esclarecido , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Segurança , Fatores de Tempo , Resultado do Tratamento
16.
Medicine (Baltimore) ; 99(35): e21825, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871904

RESUMO

OBJECTIVE: To conduct a meta-analysis evaluating the effect of combining traditional Chinese medicine (TCM) with Western medicine in treating hepatitis C, and to provide an evidence-based medical strategy. METHODS: Randomized controlled trials (RCTs) comparing the effect of pegylated interferon (Peginterferon) combined with ribavirin (PR) alone and its combination with TCM were manually retrieved from the Weipu Information Resources System (VIP), Wan Fang Database, PubMed, and the Chinese Journal Full Text Database (CNKI). Studies meeting the inclusion criteria were selected and analyzed using the Review Manager 5.3 software. Suitable tests were also performed to determine the quality, heterogeneity, and sensitivity of the studies included in the meta-analysis. RESULTS: Twenty-eight RCTs met the inclusion criteria. The combination therapy or intervention group showed significantly greater HCV-RNA negative rate post-treatment compared to the monotherapy or the control group (P < .05). In addition, the serum levels of the liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were significantly improved after the combination therapy compared to PR alone (P < .05), while total bilirubin (TB) and r-glutamyltransferase (GGT) levels were not affected by TCM (P > .05). Finally, the parameters of liver fibrosis were also reduced by the combination therapy more effectively than the monotherapy. CONCLUSION: The combination of TCM and PR can improve the Comprehensive Clinical Efficacy of hepatitis C and have a better negative rate of HCV-RNA with a better benefit in the liver function. The effect of TCM + PR is better than that of PR alone in treating hepatitis C.


Assuntos
Antivirais/uso terapêutico , Hepatite C/terapia , Medicina Tradicional Chinesa , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Terapia Combinada , Quimioterapia Combinada , Hepacivirus/genética , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Albumina Sérica , gama-Glutamiltransferase/sangue
17.
Medicine (Baltimore) ; 99(38): e22379, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957417

RESUMO

BACKGROUND: The new coronavirus-related pneumonia is causing a global pandemic without specific antiviral drug. Ribavirin has activity against extensive RNA and DNA viruses. We plan to systematically review the use of ribavirin in patients with coronavirus-related pneumonia and meta-analyze the data with updated studies. METHODS: EMBASE, PubMed, Cochrane Library, and China National Knowledge Infrastructure will be searched from 2002 to June 2021 without language restriction to identify randomized controlled trials. Subjects consist of patients with coronavirus-related pneumonia. Ribavirin of any dose or route will be compared with the control group of other medication, placebo, or no medication. The primary outcome is the hospital mortality. The secondary outcome includes the hospital length of stay, ventilator-free days in 28 days, median time from start of study treatment to negative nasopharyngeal swab, and adverse events. The Mantel-Haenszel method will be used for analysis of dichotomous data and the risk ratios will be reported with 95% confidence interval; the inverse-variance method will be used for continuous data and the mean differences will be reported. Sensitivity and subgroup analyses will be further performed. The funnel plots or Egger test will be used for detection of publication bias. The GRADE methodology will be used for summarizing the quality of evidence. The trial sequential analysis will be conducted to test whether the current meta-analysis is conclusive. RESULTS: The efficacy and safety of ribavirin for treatment of coronavirus-related pneumonia will be systematically reviewed and summarized. The forthcoming results of the ongoing studies focusing on ribavirin in patients with the 2019 noel coronavirus disease will also be included. CONCLUSION: The relevant studies will be summarized and advanced evidence will be provided. PROSPERO REGISTRATION NUMBER: CRD42020178900.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Ribavirina/uso terapêutico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/virologia , Humanos , Metanálise como Assunto , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias , Pneumonia Viral/virologia , Projetos de Pesquisa , Vírus da SARS , Síndrome Respiratória Aguda Grave/virologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
18.
Arch Virol ; 165(12): 2759-2766, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32885325

RESUMO

Oxidative stress (OS) and insulin resistance (IR) induced by hepatitis C virus (HCV) infection, are involved in the development of chronic hepatitis C (CHC) complications and progression to hepatocellular carcinoma. The aim of this study was to investigate the effect of pegylated interferon alpha (IFNα) + ribavirin (PegIFNα+RVB) or sofosbuvir + NS5A inhibitor (SOF+InNS5A) on IR and the components of OS. HCV was genotyped in 20 CHC patients grouped by treatment with either PegIFNα+RVB (n = 10) or SOF+InNS5A (n = 10). The treatment's effect on OS-induced damage to lipids (HNE-HDL), proteins (advanced glycation end products [AGEs]), and DNA (8-OHdG) as well as the concentrations of proinflammatory cytokines (IL-2, TNFα, IFNγ), ALT, AST, GSH and platelets was determined. Superoxide dismutase (SOD) and catalase activity as well as IR, determined by the HOMA1-IR index, was evaluated. The HCV genotypes (GT) found were GT1b (45%), GT1a (30%), GT2b (20%), and GT2a (5%). Viral RNA became undetectable by week 12 with SOF+InNS5A in 100% of the cases and with PegIFNα+RVB in 70% of the cases. After viral RNA became undetectable, regardless of treatment and GT, a significant increase in the platelet concentration and SOD activity was observed, whereas ALT, insulin, and IR decreased (p < 0.05). However, only for the SOF+InNS5A treated group was there an increase in oxidative damage to lipids (p < 0.017) and proteins (p < 0.05). None of the other parameters demonstrated any differences. These data confirm that OS persisted after treatment with either SOF+InNS5A or PegIFNα+RVB. IR could be considered a response biomarker to treatment with direct-acting antivirals.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Resistência à Insulina , Estresse Oxidativo/efeitos dos fármacos , RNA Viral/isolamento & purificação , Adulto , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores
19.
Brasília; s.n; 6 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117768

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 10 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Vacina BCG/uso terapêutico , Ganciclovir/uso terapêutico , Cloroquina/uso terapêutico , Estudos de Coortes , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Oseltamivir/uso terapêutico , Lopinavir/uso terapêutico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico
20.
Brasília; s.n; 11 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117979

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Ácido Ursodesoxicólico/uso terapêutico , Imunoglobulinas/uso terapêutico , Prednisolona/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Cloroquina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interferon-alfa/uso terapêutico , Tacrolimo/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Células-Tronco Mesenquimais , Lopinavir/uso terapêutico , Ácido Fólico/uso terapêutico , Meropeném/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Ácido Micofenólico/uso terapêutico
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