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1.
Pan Afr Med J ; 37: 212, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-1058635

RESUMEN

At the end of December 2019, they emerged a new coronavirus (SARS-CoV-2), triggering a pandemic of an acute respiratory syndrome (COVID-19) in humans. We report the relevant features of the first two confirmed cases of COVID-19 recorded from the 29th April 2020 in the Far North Region of Cameroon. We did a review of the files of these two patients who were admitted to the internal medicine ward of a medical Centre in Maroua Town, Far North Region. We present 2 cases of symptomatic COVID-19 patients, both males and health personnel, with an average age of 53 years, with no recent history of travel to a COVID-19 zone at risk and working in a then COVID-19 free region. They presented with extreme fatigue as their main symptom. Both were treated initially for severe malaria with quinine sulfate infusion with initial relief of symptoms. In the first confirmed case, at his re-hospitalization with an acute respiratory syndrome, a polymerase chain reaction (PCR) test in search of SARS-CoV-2 was requested with his results available 7 days into admission. For the second case, he had his results 48 hours on admission while he was prepared to be discharged. Both control PCR tests for COVID-19 came back negative 14 days after hospitalization. Health personnel remains a group at risk for the COVID-19 infection. The clinical manifestation at an early stage may be atypical mimicking endemic tropical infections. Also, the therapeutic potential of quinine salts in the relief of symptoms of COVID-19 is questionable and remains a subject to explore in our context.


Asunto(s)
/diagnóstico , Malaria/diagnóstico , Antimaláricos/administración & dosificación , Camerún , Fatiga/etiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Quinina/administración & dosificación
2.
J Antimicrob Chemother ; 76(3): 753-757, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: covidwho-990733

RESUMEN

INTRODUCTION: Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection. METHODS: This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1. RESULTS: Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001. CONCLUSIONS: In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.


Asunto(s)
Atención Ambulatoria/métodos , Antivirales/administración & dosificación , /tratamiento farmacológico , Carbamatos/administración & dosificación , Imidazoles/administración & dosificación , Pirrolidinas/administración & dosificación , Sofosbuvir/administración & dosificación , Valina/análogos & derivados , Adulto , Atención Ambulatoria/tendencias , Antimaláricos/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hidroxicloroquina/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Valina/administración & dosificación
3.
Biosci Trends ; 14(6): 408-414, 2021 Jan 23.
Artículo en Inglés | MEDLINE | ID: covidwho-979798

RESUMEN

The aim of this study is to assess the efficacy of multiple treatments, especially hydroxychloroquine, used in different disease stages of coronavirus disease 2019 (COVID-19). All consecutive patients with COVID-19 admitted to Shanghai Public Health Clinical Center (Shanghai, China) between January 20, 2020, and April 30, 2020, were enrolled, and their clinical data were retrospectively collected. Binary logistic regression was used to screen the factors associated with disease aggravation, and multivariable analyses with the Cox proportional hazards model were used to estimate the effects of prognostic factors on the improvement time and PCR conversion days in throat swabs and stool swabs. A total of 616 patients, including 50 (8.11%) severe and 18 (2.92%) critical patients, were enrolled in our retrospective cohort study. The early use of hydroxychloroquine was a protective factor associated with disease aggravation (95% CI: 0.040-0.575, p = 0.006). Clinical improvement by 20 days was significantly different between patients with hydroxychloroquine used early and those with hydroxychloroquine not used (p = 0.016, 95% CI: 1.052-1.647). The median time to clinical improvement was 6 days in the hydroxychloroquine used early group, compared with 9 days in the without hydroxychloroquine used group and 8 days in the with hydroxychloroquine not used early group (p < 0.001). Hydroxychloroquine used early was associated with earlier PCR conversion in both throat swabs (HR = 1.558, p = 0.001) and stool swabs (HR = 1.400, p = 0.028). The use of hydroxychloroquine at an early stage is a potential therapeutic strategy for treating patients before irreversible severe respiratory complications occur. The early use of hydroxychloroquine decreased the improvement time and the duration of COVID-19 detection in throat and stool swabs.


Asunto(s)
Antimaláricos/administración & dosificación , Hidroxicloroquina/administración & dosificación , Adulto , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
4.
Ciênc. Saúde Colet ; 25(9): 3517-3554, Mar. 2020. tab, graf
Artículo en Portugués | LILACS (Américas) | ID: covidwho-910849

RESUMEN

Resumo O objetivo deste trabalho foi avaliar efeitos de tratamentos medicamentosos para infecções por coronavírus. Revisão sistemática rápida com buscas nas bases MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov e International Clinical Trials Registry Platform. Foram incluídos 36 estudos avaliando alternativas medicamentosas contra SARS, SARS-CoV-2 e MERS. A maioria dos estudos incluídos foi conduzida na China com delineamento observacional para tratamento da COVID-19. Os tratamentos mais estudados foram antimaláricos e antivirais. Nos antimaláricos, a metanálise de dois estudos com 180 participantes não identificou benefício da hidroxicloroquina em relação à negativação da carga viral via reação em cadeia de polimerase em tempo real e o uso de antivirais comparado ao cuidado padrão foi similar em relação aos desfechos. As evidências científicas disponíveis são preliminares e de baixa qualidade metodológica, o que sugere cautela na interpretação dos dados. Pesquisas que avaliem a eficácia comparativa em ensaios clínicos randomizados, controlados, com tempo de acompanhamento adequado e com os métodos devidamente divulgados e sujeitos à revisão científica por pares são necessárias. Recomenda-se atualização periódica da presente revisão.


Abstract This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Antivirales/administración & dosificación , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones por Coronavirus , Infecciones por Coronavirus/virología , Síndrome Respiratorio Agudo Grave/virología , Virus del SRAS/aislamiento & purificación , Virus del SRAS/efectos de los fármacos , Pandemias , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Betacoronavirus , Betacoronavirus/aislamiento & purificación , Betacoronavirus/efectos de los fármacos , Antimaláricos/administración & dosificación
5.
J Med Case Rep ; 14(1): 210, 2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: covidwho-901919

RESUMEN

BACKGROUND: Since the World Health Organization declared a global pandemic due to the novel coronavirus disease2019, there have been targeted efforts to establish management modalities. Hydroxychloroquine has been suggested as a possible treatment; however, it is associated with multiple adverse reactions. We report a rare case of a patient with acute generalized exanthematous pustulosis with Stevens-Johnson syndrome due to hydroxychloroquine. Acute generalized exanthematous pustulosis is characterized by acute onset of a generalized rash that is pustular and erosive in nature, affecting limbs; trunk; face; and, less often, mucosal membranes. Although rare, it is important to be mindful of this side effect because the diagnosis is often delayed, and the disease has the potential to be life-threatening. CASE PRESENTATION: A 68-year-old American woman presented to our hospital with a painful, rapidly spreading rash. Its morphologic features included erythema multiforme-like lesions with extensive skin sloughing in various regions of the head, neck, and trunk and mucosal involvement. Her Nikolsky sign was negative, and she had no evidence of lesions on areas of skin trauma. Four weeks prior, she had been initiated on hydroxychloroquine for a presumed diagnosis of cutaneous sarcoidosis. Three punch biopsies of the head and neck area revealed subcorneal pustules consistent with acute generalized exanthematous pustulosis. Treatment began with high doses of methylprednisolone, leading to only minimal improvement of existing areas and ongoing spread to new areas. Treatment with intravenous immunoglobulin was initiated, at which point disease stability was achieved. The patient's rash ultimately resolved, as did her cutaneous pain and pruritus. CONCLUSIONS: Among many potential adverse reactions involving hydroxychloroquine, cutaneous side effects are varied and can lead to significant morbidity or even death. The drug is currently being investigated in a multitude of trials for coronavirus disease2019 treatment, prevention, and prophylaxis after exposure to severe acute respiratory syndrome coronavirus 2. Acute generalized exanthematous pustulosis is a rare side effect of hydroxychloroquine, and even fewer cases demonstrate histologic evidence of acute generalized exanthematous pustulosis while clinically presenting with Stevens-Johnson syndrome. Patients who develop Stevens-Johnson syndrome/toxic epidermal necrolysis require best supportive care with aggressive fluid and electrolyte replacement and prevention of further breakdown of the skin barrier. With the potential of widespread hydroxychloroquine use, it is important that providers be aware of its potential severe adverse drug reactions.


Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Infecciones por Coronavirus/epidemiología , Hidroxicloroquina , Inmunoglobulinas Intravenosas/administración & dosificación , Metilprednisolona/administración & dosificación , Neumonía Viral/epidemiología , Sarcoidosis/tratamiento farmacológico , Síndrome de Stevens-Johnson , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/fisiopatología , Pustulosis Exantematosa Generalizada Aguda/terapia , Anciano , Antimaláricos/administración & dosificación , Antimaláricos/efectos adversos , Biopsia/métodos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Factores Inmunológicos , Pandemias , Piel/patología , Enfermedades de la Piel/tratamiento farmacológico , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/fisiopatología , Síndrome de Stevens-Johnson/terapia , Resultado del Tratamiento
6.
Trials ; 21(1): 866, 2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: covidwho-883593

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Ribavirina/uso terapéutico , Administración Oral , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Antivirales/administración & dosificación , Betacoronavirus/genética , Protocolos Clínicos , Terapia Combinada , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A/uso terapéutico , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , India/epidemiología , Consentimiento Informado , Lopinavir/administración & dosificación , Lopinavir/uso terapéutico , Masculino , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Ribavirina/administración & dosificación , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico , Seguridad , Factores de Tiempo , Resultado del Tratamiento
7.
Bol Med Hosp Infant Mex ; 77(5): 242-251, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-859322

RESUMEN

Since December 2019, health systems worldwide have faced the pandemic caused by the new severe acute respiratory syndrome coronavirus 2. The pandemic began in China and has spread throughout the world. This new coronavirus has a high transmission capacity and elevated lethality in people over 60 years old and in those with risk factors (obesity, diabetes, and systemic arterial hypertension); those characteristics have a different proportion in each country. At present, there is no specific, effective, and safe treatment to treat this virus. In this review, an analysis is made on the differences in epidemiological aspects of the disease and its presentation in pediatric patients; the poorly-based recommendation for using an empirical combination of antimalarials plus antimicrobials as antiviral treatment; the indication of intravenous steroids; and the possible influence of antihypertensive drugs on the course of the disease.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Factores de Edad , Antimaláricos/administración & dosificación , Antivirales/administración & dosificación , Niño , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Factores de Riesgo
8.
Ciênc. Saúde Colet ; 25(9): 3517-3554, Mar. 2020. tab, graf
Artículo en Portugués | LILACS (Américas) | ID: covidwho-853600

RESUMEN

Resumo O objetivo deste trabalho foi avaliar efeitos de tratamentos medicamentosos para infecções por coronavírus. Revisão sistemática rápida com buscas nas bases MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov e International Clinical Trials Registry Platform. Foram incluídos 36 estudos avaliando alternativas medicamentosas contra SARS, SARS-CoV-2 e MERS. A maioria dos estudos incluídos foi conduzida na China com delineamento observacional para tratamento da COVID-19. Os tratamentos mais estudados foram antimaláricos e antivirais. Nos antimaláricos, a metanálise de dois estudos com 180 participantes não identificou benefício da hidroxicloroquina em relação à negativação da carga viral via reação em cadeia de polimerase em tempo real e o uso de antivirais comparado ao cuidado padrão foi similar em relação aos desfechos. As evidências científicas disponíveis são preliminares e de baixa qualidade metodológica, o que sugere cautela na interpretação dos dados. Pesquisas que avaliem a eficácia comparativa em ensaios clínicos randomizados, controlados, com tempo de acompanhamento adequado e com os métodos devidamente divulgados e sujeitos à revisão científica por pares são necessárias. Recomenda-se atualização periódica da presente revisão.


Abstract This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Antivirales/administración & dosificación , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones por Coronavirus , Infecciones por Coronavirus/virología , Síndrome Respiratorio Agudo Grave/virología , Virus del SRAS/aislamiento & purificación , Virus del SRAS/efectos de los fármacos , Pandemias , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Betacoronavirus , Betacoronavirus/aislamiento & purificación , Betacoronavirus/efectos de los fármacos , Antimaláricos/administración & dosificación
9.
Eur J Drug Metab Pharmacokinet ; 45(6): 703-713, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: covidwho-784916

RESUMEN

BACKGROUND AND OBJECTIVE: In the absence of characterization on pharmacokinetics and reference concentrations for hydroxychloroquine in COVID-19 patients, the dose and treatment duration for hydrochloroquine are currently empirical, mainly based on in vitro data, and may vary across national guidelines and clinical study protocols. The aim of this paper is to describe the pharmacokinetics of hydroxychloroquine in COVID-19 patients, considered to be a key step toward its dosing optimization. METHODS: We have developed a population pharmacokinetic model for hydroxychloroquine in COVID-19 patients using prospectively collected pharmacokinetic data from patients either enrolled in a clinical trial or treated with hydroxychloroquine as part of standard of care in two tertiary Belgian hospitals. RESULTS: The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination. The estimated parameter values were 9.3/h, 860.8 L, and 15.7 L/h for the absorption rate constant, the central compartment volume, and the clearance, respectively. The bioavailability factor was fixed to 0.74 based on previously published models. Model validations by bootstraps, prediction corrected visual predictive checks, and normalized prediction distribution errors gave satisfactory results. Simulations were performed to compare the exposure obtained with alternative dosing regimens. CONCLUSION: The developed models provide useful insight for the dosing optimization of hydroxychloroquine in COVID-19 patients. The present results should be used in conjunction with exposure-efficacy and exposure-safety data to inform optimal dosing of hydroxychloroquine in COVID-19.


Asunto(s)
Antimaláricos/administración & dosificación , Antimaláricos/farmacocinética , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/farmacocinética , Neumonía Viral/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Disponibilidad Biológica , Infecciones por Coronavirus/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/metabolismo , Adulto Joven
10.
Ann Am Thorac Soc ; 17(9): 1144-1153, 2020 09.
Artículo en Inglés | MEDLINE | ID: covidwho-781684

RESUMEN

The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including 1) widespread, off-label use of the study drug before the availability of safety and efficacy data; 2) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; 3) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; 4) obtaining indistinguishable drug and placebo without delaying enrollment; and 5) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.Clinical trial registered with www.clinicaltrials.gov (NCT04332991).


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Pandemias , Neumonía Viral/tratamiento farmacológico , Adulto , Antimaláricos/administración & dosificación , Infecciones por Coronavirus/epidemiología , Relación Dosis-Respuesta a Droga , Hospitalización/tendencias , Humanos , Neumonía Viral/epidemiología , Método Simple Ciego , Resultado del Tratamiento
12.
J Bras Nefrol ; 42(2 suppl 1): 49-50, 2020 Aug 26.
Artículo en Inglés, Portugués | MEDLINE | ID: covidwho-740468

RESUMEN

Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.


Asunto(s)
Antimaláricos/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Insuficiencia Renal , Brasil , Humanos , Nefrología , Pandemias , Sociedades Médicas
13.
Cien Saude Colet ; 25(9): 3517-3554, 2020 Sep.
Artículo en Inglés, Portugués | MEDLINE | ID: covidwho-740424

RESUMEN

This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Antimaláricos/administración & dosificación , Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Pandemias , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Virus del SRAS/efectos de los fármacos , Virus del SRAS/aislamiento & purificación , Síndrome Respiratorio Agudo Grave/virología
14.
PLoS One ; 15(8): e0237831, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-725099

RESUMEN

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/virología , Darunavir/uso terapéutico , Femenino , Estudios de Seguimiento , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Ritonavir/uso terapéutico , Resultado del Tratamiento
15.
J Interv Card Electrophysiol ; 59(2): 337-345, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: covidwho-640049

RESUMEN

PURPOSE: Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients. METHODS: We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias. RESULTS: One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7). Adjusting for race/ethnicity yielded no significant associations. CONCLUSIONS: Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.


Asunto(s)
Antimaláricos/efectos adversos , Azitromicina/efectos adversos , Infecciones por Coronavirus/tratamiento farmacológico , Electrocardiografía/métodos , Síndrome de QT Prolongado/inducido químicamente , Neumonía Viral/tratamiento farmacológico , Distribución por Edad , Anciano , Anciano de 80 o más Años , Antimaláricos/administración & dosificación , Azitromicina/administración & dosificación , Cloroquina/administración & dosificación , Cloroquina/efectos adversos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Incidencia , Síndrome de QT Prolongado/diagnóstico por imagen , Síndrome de QT Prolongado/tratamiento farmacológico , Síndrome de QT Prolongado/epidemiología , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Pandemias/estadística & datos numéricos , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Medición de Riesgo , Distribución por Sexo , Población Urbana
16.
Elife ; 92020 07 08.
Artículo en Inglés | MEDLINE | ID: covidwho-636307

RESUMEN

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.


Asunto(s)
Cloroquina/envenenamiento , Sobredosis de Droga/mortalidad , Intento de Suicidio , Suicidio , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/envenenamiento , Antimaláricos/uso terapéutico , Biotransformación , Cloroquina/administración & dosificación , Cloroquina/efectos adversos , Cloroquina/análogos & derivados , Cloroquina/sangre , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Reposicionamiento de Medicamentos , Electrocardiografía , Femenino , Cardiopatías/inducido químicamente , Cardiopatías/mortalidad , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/envenenamiento , Hidroxicloroquina/uso terapéutico , Síndrome de QT Prolongado/inducido químicamente , Malaria/tratamiento farmacológico , Masculino , Pandemias , Neumonía Viral/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Medición de Riesgo
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