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1.
Eur Rev Med Pharmacol Sci ; 25(1): 549-555, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33506948

RESUMO

OBJECTIVE: Because of the limited treatment options available, oral lopinavir/ritonavir (LPR) was used for treating coronavirus disease (COVID-19) in pediatric patients. This study aimed to assess the efficacy and safety of LPR in COVID-19 pediatric patients with mild symptoms. PATIENTS AND METHODS: This retrospective multicenter analysis included hospitalized children with mild COVID-19 who received LPR at one of 13 hospitals in China from January 1, 2020, to June 1, 2020. Patients treated with LPR were matched with patients not treated with LPR (1:4) according to age, sex, and length of symptom onset and hospitalization. Descriptive statistics and non-parametric tests were applied to compare differences between groups. Kaplan-Meier probability curves and Cox regression models were used to analyze nasal swab turning negative time (recovery time) and hospital discharge days. RESULTS: In total, 23 patients treated with LPR were matched with 92 untreated controls. The median age of patients was 6 years, and 56.52% of them were male. All patients were discharged from the hospital after being cured. The treatment group had a longer nasal swab turning negative time (hazard ratio [HR] 5.33; 95% CI: 1.94-14.67; p = 0.001) than the control group. LPR treatment was also associated with a longer hospitalization time (HR 2.01; 95% CI: 1.24-3.29; p = 0.005). After adjusting for the influence of LPR treatment, adverse drug reaction events were associated with a longer nasopharyngeal swab negative time (HR 4.67; 95% CI 1.35-16.11; p = 0.015). CONCLUSIONS: For children with mild COVID-19, LPR is inferior to conventional treatment in reducing virus shedding time and hospitalization duration and is associated with increased adverse reactions.


Assuntos
Antivirais/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Administração Oral , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , China , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Estudos Retrospectivos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
2.
Sci Rep ; 11(1): 2169, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500507

RESUMO

To evaluate the predictive effect of T-lymphoid subsets on the conversion of common covid-19 to severe. The laboratory data were collected retrospectively from common covid-19 patients in the First People's Hospital of Zaoyang, Hubei Province, China and the Third People's Hospital of Kunming, Yunnan Province, China, between January 20, 2020 and March 15, 2020 and divided into training set and validation set. Univariate and multivariate logistic regression was performed to investigate the risk factors for the conversion of common covid-19 to severe in the training set, the prediction model was established and verified externally in the validation set. 60 (14.71%) of 408 patients with common covid-19 became severe in 6-10 days after diagnosis. Univariate and multiple logistic regression analysis revealed that lactate (P = 0.042, OR = 1097.983, 95% CI 1.303, 924,798.262) and CD8+ T cells (P = 0.010, OR = 0.903, 95% CI 0.835, 0.975) were independent risk factors for general type patients to turn to severe type. The area under ROC curve of lactate and CD8+ T cells was 0.754 (0.581, 0.928) and 0.842 (0.713, 0.970), respectively. The actual observation value was highly consistent with the prediction model value in curve fitting. The established prediction model was verified in 78 COVID-19 patients in the verification set, the area under the ROC curve was 0.906 (0.861, 0.981), and the calibration curve was consistent. CD8+ T cells, as an independent risk factor, could predict the transition from common covid-19 to severe.


Assuntos
Linfócitos T CD8-Positivos/virologia , Progressão da Doença , Corticosteroides/administração & dosagem , Adulto , Algoritmos , China , Feminino , Humanos , Hipóxia/metabolismo , Lopinavir/administração & dosagem , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Oxigênio/química , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Ritonavir/administração & dosagem
3.
Trials ; 22(1): 4, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397429

RESUMO

OBJECTIVES: We will evaluate the efficacy and safety of Ivermectin in patients with mild and moderately severe COVID-19. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design (1:1 ratio). PARTICIPANTS: The Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will screen for patients age ≥ 20 years and weight ≥35 kg for the following criteria: Inclusion criteria for patients with mild COVID-19 symptoms (outpatients) 1. Diagnosed mild pneumonia using computed tomography (CT) and/or chest X-ray (CX-R) imaging, not requiring hospitalization. 2. Signing informed consent. Inclusion criteria for patients with moderate COVID-19 symptoms (inpatients) 1. Confirmed infection using PCR. 2. Diagnosed moderate pneumonia using CT and/or CXR imaging, requiring hospitalization. 3. Hospitalized ≤ 48 hours. 4. Signing informed consent. Exclusion criteria 1. Severe and critical pneumonia due to COVID-19. 2. Underlying diseases, including AIDS, asthma, loiasis, and severe liver and kidney disease. 3. Use of anticoagulants (e.g., warfarin) and ACE inhibitors (e.g., captopril). 4. History of drug allergy to Ivermectin. 5. Pregnancy or breastfeeding. INTERVENTION AND COMPARATOR: Intervention groups: Outpatient and inpatient groups will receive the standard treatment regimen for mild and moderate COVID-19, based on the Iranian Ministry of Health and Medical Education's protocol, along with oral Ivermectin (MSD Company, France) at a single dose of 0.2 mg/kg. Control groups: The outpatient group will receive hydroxychloroquine sulfate (Amin Pharmaceutical Company, Iran) at a dose of 400 mg twice a day for the first day and 200 mg twice a day for seven subsequent days. The inpatient group will receive 200/50 mg Lopinavir/Ritonavir (Heterd Company, India) twice a day for the seven days, plus five doses of 44 mcg Interferon beta-1a (CinnaGen, Iran) every other day. Other supportive and routine care will be the same in both outpatient and inpatient groups. MAIN OUTCOME: The primary outcomes are composite and include the improvement of clinical symptoms and need for hospitalization for outpatient groups, and the length of hospital stay until discharge, the need for ICU admission until discharge, and the need for mechanical ventilation for inpatient groups within seven days of randomization. The secondary outcome is the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Patients in both outpatient (mild) and inpatient (moderate) groups will be randomized into the treatment and control groups based on the following method. A simple randomization method and table of random numbers will be used. If the selected number is even, the patient is allocated to the treatment group, and if it is odd, the patient is allocated to the control group in a 1:1 ratio. BLINDING (MASKING): This is an open-label study, and there is not blinding. Numbers to be randomized (sample size) A total number of 120 patients (60 outpatients and 60 patients) will be randomized into two groups (30 patients in each of the intervention groups and 30 patients in each of the control groups). TRIAL STATUS: The protocol is Version 1.0, November 17, 2020. Recruitment began November 25, 2020, and is anticipated to be completed by February 25, 2021. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N6 ". The registration date is November 17, 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 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.


Assuntos
Antivirais/administração & dosagem , Ivermectina/administração & dosagem , /isolamento & purificação , Administração Oral , Adulto , Antivirais/efeitos adversos , /virologia , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Unidades de Terapia Intensiva/estatística & dados numéricos , Interferon beta-1a/administração & dosagem , Interferon beta-1a/efeitos adversos , Irã (Geográfico) , Ivermectina/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Índice de Gravidade de Doença
4.
Int Immunopharmacol ; 92: 107329, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33412395

RESUMO

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.


Assuntos
Antivirais/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Combinação de Medicamentos , Feminino , Humanos , Interferon beta/administração & dosagem , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/administração & dosagem , Adulto Jovem
5.
Ann Intern Med ; 174(1): JC3, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395331

RESUMO

SOURCE CITATION: RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396:1345-52. 33031764.


Assuntos
Antivirais/uso terapêutico , Hospitalização , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Administração Oral , Idoso , Antivirais/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Lopinavir/administração & dosagem , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/administração & dosagem , Reino Unido
6.
J Interferon Cytokine Res ; 40(12): 578-588, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33337933

RESUMO

A previous report on 814 patients who were coronavirus disease 2019 (COVID-19) positive provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) in Cuba, from March 11 to April 14, 2020. This study re-evaluates the effectiveness of IFN-α2b during the period from March 11 to June 17, 2020. Patients received a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b. The primary endpoint was the proportion of patients discharged from the hospital; the secondary endpoint was the case fatality rate, and several outcomes related to time variables were also evaluated. From March 11 to June 17, 2,295 patients had been confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive in Cuba, 2,165 were treated with Heberon® Alpha R, and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with the non-IFN-treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. Benefits of IFN were significantly supported by time variables analyzed. This second report confirmed our preliminary evidence about the therapeutic effectiveness of IFN-α2b in SARS-CoV-2 infection and postulated Heberon Alpha R as the main component within antiviral drugs used in the Cuban protocol COVID-19.


Assuntos
/terapia , Interferon alfa-2/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cloroquina/administração & dosagem , Comorbidade , Cuidados Críticos , Cuba/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
7.
Swiss Med Wkly ; 150: w20446, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33382449

RESUMO

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.


Assuntos
Antivirais/uso terapêutico , /epidemiologia , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , Pré-Escolar , Comorbidade , Combinação de Medicamentos , Quimioterapia Combinada , Gastos em Saúde , Mortalidade Hospitalar/tendências , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lactente , Tempo de Internação/estatística & dados numéricos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Terapias em Estudo/métodos , Adulto Jovem
8.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33372741
9.
Reumatismo ; 72(3): 173-177, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213130

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adalimumab/administração & dosagem , Adulto , Antivirais/administração & dosagem , Artrite Reumatoide/complicações , Azatioprina/administração & dosagem , Terapia Biológica , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Lopinavir/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Oseltamivir/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prednisolona/administração & dosagem , Ritonavir/administração & dosagem
10.
Trials ; 21(1): 880, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106183

RESUMO

OBJECTIVES: We will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease TRIAL DESIGN: This is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial. PARTICIPANTS: The eligibility criteria in this study is: age ≥ 18 years, oxygen saturation (SPO2) ≤ 93% or respiratory rate ≥ 24, at least one of the following manifestation: radiation contactless body temperature ≥37.8, Cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (≤ 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir/ritonavir or interferon-ß 1a, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences. INTERVENTION AND COMPARATOR: COVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir / ritonavir (Kaletra) + high dose Interferon-ß 1a (Recigen) and the control group will be treated with lopinavir / ritonavir (Kaletra) + low dose Interferon-ß 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation. MAIN OUTCOMES: Primary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. SECONDARY OUTCOMES: mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. RANDOMIZATION: Eligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Of the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir/ritonavir (Kaletra). TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20th 2020, and the end date was on September 4th 2020. Last point of data collection will be the last day on which all of the 100 participants have had an outcome of clinical improvement or death, up to 14th days after hospitalization. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials ( www.clinicaltrials.gov ; identification number NCT04521400, https://clinicaltrials.gov/ct2/show/NCT04521400 , registered August 18, 2020 and first available online August 20, 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 , Interferon beta-1a/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Antivirais/administração & dosagem , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Humanos , Interferon beta-1a/administração & dosagem , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Mortalidade/tendências , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Alta do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Respiração Artificial/estatística & dados numéricos , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico
11.
Trials ; 21(1): 886, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109246

RESUMO

OBJECTIVES: We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. INCLUSION CRITERIA: 1. Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. 2. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. 3. Hospitalized ≤ 48 h. 4. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. 2. Severe and critical COVID-19 pneumonia. 3. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. 4. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day. CONTROL GROUP: lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups. MAIN OUTCOMES: The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O2 saturation within 7 days of randomization. The secondary outcomes are the length of hospital stay and the incidence of serious adverse drug reactions within 7 days of randomization. RANDOMIZATION: Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group). TRIAL STATUS: The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3 . Registered on 22 July 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 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.


Assuntos
Amidas , Infecções por Coronavirus , Quimioterapia Combinada/métodos , Interferons , Lopinavir , Pandemias , Pneumonia Viral , Pirazinas , Ritonavir , Adulto , Amidas/administração & dosagem , Amidas/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Interferons/administração & dosagem , Interferons/efeitos adversos , Irã (Geográfico) , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Viral/métodos
12.
Medicine (Baltimore) ; 99(43): e22920, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120844

RESUMO

RATIONALE: Reversible splenial lesion syndrome (RESLES) is a recently identified clinico-radiological syndrome, the etiology is miscellaneous. Atrial septal defect (ASD) as an underlying etiology for RESLES has not been reported. We first report a rare case of RESLES associated with ASD. The clinical, radiological, and ultrasonic profiles were presented and the pathophysiological mechanism was analyzed. PATIENT CONCERNS: A 23-year-old man presented with headache, drowsiness, occasional paraphasia, and paroxysmal dry cough. Brain magnetic resonance imaging (MRI) on admission showed an ovoid isolated lesion in the splenium of corpus callosum, which exhibited hyperintensity on diffusion-weighted imaging and hypointensity on apparent diffusion coefficient, and completely disappeared on the follow-up MRI 14 days later. ASD was found by transthoracic echocardiography, Right-to-left shunts were detected on color Doppler of transesophageal echocardiography, and microemboli were captured by transcranial Doppler ultrasound. DIAGNOSES: According to his clinical history and imaging results, we confirmed the diagnosis of RESLES associated with ASD. INTERVENTIONS: The patient was treated by oral aspirin and lopidogrel sulfate to inhibit platelet aggregation. In addition, oral nimodipine to suppress vasoconstriction. OUTCOMES: After 14 days treatment, all the symptoms presenting on admission resolved completely. Subsequently, a repair surgery of ASD under thoracoscopy was successfully performed. LESSONS: To our knowledge, this is the first reported case of ASD may be an underlying etiology for RESLES and need require an etiotropic treatment.


Assuntos
Encefalopatias/etiologia , Corpo Caloso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Comunicação Interatrial/complicações , Administração Oral , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Corpo Caloso/patologia , Combinação de Medicamentos , Quimioterapia Combinada , Ecocardiografia/métodos , Seguimentos , Cefaleia/etiologia , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/tratamento farmacológico , Comunicação Interatrial/cirurgia , Humanos , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Masculino , Nimodipina/administração & dosagem , Nimodipina/uso terapêutico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Síndrome , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana/métodos , Adulto Jovem
13.
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
14.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871902

RESUMO

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.


Assuntos
Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus , Exantema , Glucocorticoides/administração & dosagem , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pandemias , Pneumonia Viral , Ritonavir/administração & dosagem , Administração Tópica , Adulto , Antivirais/administração & dosagem , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Exantema/diagnóstico , Exantema/tratamento farmacológico , Exantema/etiologia , Exantema/imunologia , Feminino , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Avaliação de Sintomas/métodos , Resultado do Tratamento
15.
J Infect Chemother ; 26(12): 1319-1323, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32893123

RESUMO

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Guanidinas/administração & dosagem , Hemodiafiltração/métodos , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Antivirais/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Japão , Lopinavir/administração & dosagem , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Insuficiência Respiratória/complicações , Ritonavir/administração & dosagem , Resultado do Tratamento
16.
J Gastrointestin Liver Dis ; 29(3): 473-475, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32919428
17.
Toxicol Appl Pharmacol ; 406: 115237, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920000

RESUMO

Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.


Assuntos
Betacoronavirus , Simulação por Computador , Mineração de Dados/métodos , Toxicogenética/métodos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Bases de Dados Genéticas , Quimioterapia Combinada , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
18.
Med. clín (Ed. impr.) ; 155(5): 202-204, sept. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188495

RESUMO

ANTECEDENTES Y OBJETIVO: La pandemia por Covid-19 afecta especialmente a pacientes con cáncer con mayor incidencia y mortalidad según series publicadas de focos originales de pandemia. El estudio pretende conocer la mortalidad en nuestro centro por covid-19 en pacientes con cáncer durante las primeras3 semanas de epidemia. MATERIAL Y MÉTODOS: Se han revisado los pacientes con cáncer fallecidos por covid-19 durante el periodo de análisis describiendo las características oncológicas, de la infección por covid-19 y de los tratamientos instaurados. RESULTADOS: Casos confirmados covid-19: 1069 con 132 fallecimientos (12,3%). Con cáncer 36 pacientes (3.4%), 15 fallecidos (41,6%). De los fallecidos solo6 pacientes (40%) se encontraban en tratamiento activo. El tumor más frecuente asociado fue pulmón (8/15 pacientes, 53,3%), 11 con enfermedad metastásica (11/15, 73,3%). El 40% (6/15) no recibió tratamiento específico contra covid-19, el resto fue tratado con los protocolos activos. CONCLUSIÓN: La mortalidad por covid-19 en pacientes con cáncer casi cuadriplica la de la población general. Hasta disponer de tratamientos eficaces o una vacuna efectiva la única posibilidad de proteger a nuestros pacientes es impedir el contagio con las medidas adecuadas


BACKGROUND AND OBJECTIVE: The Covid-19 pandemic especially affects cancer patients with higher incidence and mortality according to published series of original pandemic foci. The study aims to determine the mortality in our center due to covid-19 in cancer patients during the first 3 weeks of the epidemic. MATERIAL AND METHODS: The cancer patients who died of covid-19 during the analysis period have been reviewed describing the oncological and the covid-19 infection characteristics and the treatments established. RESULTS: Confirmed cases covid-19: 1069 with 132 deaths (12.3%). With cancer 36 patients (3.4%), 15 deceased (41.6%). Of the deceased, only 6 patients (40%) were in active treatment. The most frequent associated tumor was lung (8/15 patients, 53.3%), 11 with metastatic disease (11/15, 73.3%). No specific treatment wasestablished in 40 % (6/15) of the patients. The rest of them received treatments with the active protocols. CONCLUSION: Covid-19 mortality in cancer patients is almost four times higher than that of the general population. Until we have effective treatments or an effective vaccine, the only possibility to protect our patients is to prevent the infection with the appropriate measures


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/mortalidade , Neoplasias/epidemiologia , Comorbidade , Neoplasias/complicações , Febre/complicações , Tosse/complicações , Dispneia/complicações , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Azitromicina/administração & dosagem , Antineoplásicos/administração & dosagem , Unidades de Terapia Intensiva/estatística & dados numéricos
19.
Int J Antimicrob Agents ; 56(4): 106142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853675

RESUMO

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.


Assuntos
Anti-Infecciosos/administração & dosagem , Azitromicina/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Ritonavir/administração & dosagem , Idoso , Anti-Infecciosos/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Unidades de Terapia Intensiva , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Lopinavir/efeitos adversos , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Ritonavir/efeitos adversos , Resultado do Tratamento , Troponina I/sangue
20.
Am J Gastroenterol ; 115(10): 1716-1718, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32858566

RESUMO

INTRODUCTION: We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus. METHODS: This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group. RESULTS: Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%). DISCUSSION: Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Icterícia/induzido quimicamente , Lopinavir/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Ritonavir/efeitos adversos , Idoso , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Icterícia/diagnóstico , Icterícia/epidemiologia , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Estudos Prospectivos , Estudos Retrospectivos , Ritonavir/administração & dosagem , Índice de Gravidade de Doença , Padrão de Cuidado/estatística & dados numéricos
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