Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 125
Filtrar
Añadir filtros

Intervalo de año
1.
Medwave ; 20(7): e8008, 2020 Aug 28.
Artículo en Español | MEDLINE | ID: covidwho-740553

RESUMEN

In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.


Asunto(s)
Betacoronavirus , Enfermedades Cardiovasculares/complicaciones , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/terapia , Algoritmos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antivirales/efectos adversos , Azitromicina/efectos adversos , Infecciones por Coronavirus/tratamiento farmacológico , Quimioterapia Combinada , Electrocardiografía/efectos de los fármacos , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Hidroxicloroquina/efectos adversos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/tratamiento farmacológico , Pronóstico , Sistema Renina-Angiotensina/fisiología
4.
Open Heart ; 7(2)2020 08.
Artículo en Inglés | MEDLINE | ID: covidwho-725618

RESUMEN

The outbreak of COVID-19 in Wuhan, China and its declaration as a global pandemic by WHO has left the medical community under significant pressure to rapidly identify effective therapeutic and preventative strategies. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were found to be efficacious against SARS-CoV-2 when investigated in preliminary in vitro experiments. Reports of success in early clinical studies were widely publicised by news outlets, politicians and on social media. These results led several countries to approve the use of these drugs for the treatment of patients with COVID-19. Despite having reasonable safety profiles in the treatment of malaria and certain autoimmune conditions, both drugs are known to have potential cardiotoxic side effects. There is a high incidence of myocardial injury and arrhythmia reported with COVID-19 infection, and as such this population may be more susceptible to this side-effect profile. Studies to date have now demonstrated that in patients with COVID-19, these drugs are associated with significant QTc prolongation, as well as reports of ventricular arrhythmias. Furthermore, subsequent studies have failed to demonstrate clinical benefit from either drug. Indeed, clinical trials have also been stopped early due to safety concerns over HCQ. There is an urgent need for credible solutions to the global pandemic, but we argue that in the absence of high-quality evidence, there needs to be greater caution over the routine use or authorisation of drugs for which efficacy and safety is unproven.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Electrocardiografía/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Neumonía Viral/tratamiento farmacológico , Medición de Riesgo , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Infecciones por Coronavirus/epidemiología , Salud Global , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Incidencia , Síndrome de QT Prolongado/fisiopatología , Pandemias , Neumonía Viral/epidemiología
5.
Ann Am Thorac Soc ; 17(8): 1008-1015, 2020 08.
Artículo en Inglés | MEDLINE | ID: covidwho-724110

RESUMEN

Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especially within the global context of related studies, may also foster collaborative relationships among government, community, and the research enterprise. Here, we describe the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and nonacademic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We used a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for interpreting the range of possible results from this trial within the context of parallel trials and prepared for a network meta-analysis of the resulting data. This trial was prospectively registered (ClinicalTrials.gov Identifier: NCT04329832) before enrollment of the first patient.Clinical trial registered with www.clinicaltrials.gov (NCT04329832).


Asunto(s)
Azitromicina , Infecciones por Coronavirus , Hidroxicloroquina , Pandemias , Neumonía Viral , Adulto , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Monitoreo de Drogas/métodos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Masculino , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Utah
7.
J Med Internet Res ; 22(8): e20007, 2020 08 17.
Artículo en Inglés | MEDLINE | ID: covidwho-721428

RESUMEN

BACKGROUND: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance. OBJECTIVE: We aimed to evaluate whether RMA can generate meaningful clinical insights, but crucially, in a much faster processing time than traditional meta-analysis, using a relevant, real-world example. METHODS: The development of our RMA approach was motivated by a currently relevant clinical question: is ocular toxicity and vision compromise a side effect of hydroxychloroquine therapy? At the time of designing this study, hydroxychloroquine was a leading candidate in the treatment of coronavirus disease (COVID-19). We then leveraged AI to pull and screen articles, automatically extract their results, review the studies, and analyze the data with standard statistical methods. RESULTS: By combining AI with human analysis in our RMA, we generated a meaningful, clinical result in less than 30 minutes. The RMA identified 11 studies considering ocular toxicity as a side effect of hydroxychloroquine and estimated the incidence to be 3.4% (95% CI 1.11%-9.96%). The heterogeneity across individual study findings was high, which should be taken into account in interpretation of the result. CONCLUSIONS: We demonstrate that a novel approach to meta-analysis using AI can generate meaningful clinical insights in a much shorter time period than traditional meta-analysis.


Asunto(s)
Inteligencia Artificial , Infecciones por Coronavirus/tratamiento farmacológico , Oftalmopatías/etiología , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Metaanálisis como Asunto , Neumonía Viral/tratamiento farmacológico , Ojo/efectos de los fármacos , Ojo/patología , Humanos , Pandemias , Factores de Tiempo
8.
J Med Internet Res ; 22(9): e21758, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: covidwho-714139

RESUMEN

BACKGROUND: During the initial phases of the COVID-19 pandemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ) and tocilizumab (TCZ); however, evidence on their efficacy and safety have been controversial. OBJECTIVE: The purpose of this study is to evaluate the overall clinical effectiveness of HCQ and TCZ in patients with COVID-19. We hypothesize that HCQ and TCZ use in these patients will be associated with a reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. METHODS: A retrospective cohort study was performed to determine the impact of HCQ and TCZ use on hard clinical outcomes during hospitalization. A total of 176 hospitalized patients with a confirmed COVID-19 diagnosis was included. Patients were divided into two comparison groups: (1) HCQ (n=144) vs no-HCQ (n=32) and (2) TCZ (n=32) vs no-TCZ (n=144). The mean age, baseline comorbidities, and other medications used during hospitalization were uniformly distributed among all the groups. Independent t tests and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios with 95% CIs, respectively. RESULTS: The unadjusted odds ratio for patients upgraded to a higher level of care (ie, intensive care unit) (OR 2.6, 95% CI 1.19-5.69; P=.003) and reductions in C-reactive protein (CRP) level on day 7 of hospitalization (21% vs 56%, OR 0.21, 95% CI 0.08-0.55; P=.002) were significantly higher in the TCZ group compared to the control group. There was no significant difference in the odds of in-hospital mortality, upgrade to intensive medical care, need for invasive mechanical ventilation, acute kidney failure necessitating dialysis, or discharge from the hospital after recovery in both the HCQ and TCZ groups compared to their respective control groups. Adjusted odds ratios controlled for baseline comorbidities and medications closely followed the unadjusted estimates. CONCLUSIONS: In this cohort of patients with COVID-19, neither HCQ nor TCZ offered a significant reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. These results are similar to the recently published preliminary results of the HCQ arm of the Recovery trial, which showed no clinical benefit from the use of HCQ in hospitalized patients with COVID-19 (the TCZ arm is ongoing). Double-blinded randomized controlled trials are needed to further evaluate the impact of these drugs in larger patient samples so that data-driven guidelines can be deduced to combat this global pandemic.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/mortalidad , Mortalidad Hospitalaria , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/mortalidad , Anciano , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/farmacología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pandemias , Estudios Retrospectivos , Resultado del Tratamiento
10.
West J Emerg Med ; 21(4): 760-763, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: covidwho-690721

RESUMEN

As of April 21, 2020, more than 2.5 million cases of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, have been reported in 210 countries and territories, with the death toll at 171,810. Both chloroquine and hydroxychloroquine have gained considerable media attention as possible therapies, resulting in a significant surge in demand. In overdose, both medications can cause severe, potentially life-threatening effects. Here, we present a brief overview of the pharmacology of chloroquine and hydroxychloroquine, manifestations of toxicity, and treatment considerations.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Cloroquina/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Pandemias
11.
Trials ; 21(1): 688, 2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: covidwho-684349

RESUMEN

OBJECTIVES: The aim of this study is to assess the efficacy of the use of pre-exposure prophylaxis (PrEP) with hydroxychloroquine against placebo in healthcare workers with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in reducing their risk of coronavirus disease 2019 (COVID-19) disease during an epidemic period. As secondary objectives, we would like to: i) assess the efficacy of the use of PrEP with hydroxychloroquine against placebo in healthcare workers with high risk of SARS-CoV-2 infection in reducing their risk of exposure to SARS-CoV-2 (defined by seroconversion) during an epidemic period, ii) evaluate the safety of PrEP with hydroxychloroquine in adults, iii) describe the incidence of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 infection, iv) identify clinical, analytical and microbiological predictors of COVID-19 among healthcare workers at high risk of SARS-CoV-2 infection, v) set up a repository of serum samples obtained from healthcare workers at high risk of SARS-CoV-2 infection for future research on blood markers to predict SARS-CoV-2 infection. TRIAL DESIGN: Multicentre double-blind parallel design (ratio 1:1) randomized controlled clinical trial. PARTICIPANTS: Approximately 440 healthcare workers of four Spanish hospitals (Hospital Clínic of Barcelona, Hospital de la Santa Creu i Sant Pau of Barcelona, Hospital Plató of Barcelona, Hospital General de Granollers, Barcelona) will be recruited. Participants are considered to be at high-risk of SARS-CoV-2 infection due to their frequent contact with suspected and confirmed cases of COVID-19. For eligibility, healthcare workers with 18 years old or older working at least 3 days a week in a hospital with both negative SARS-CoV-2 polymerase chain reaction (PCR) assays and serological COVID-19 rapid diagnostic tests (RDT) are invited to participate. Participants with any of the following conditions are excluded: pregnancy, breastfeeding, ongoing antiviral, antiretroviral or corticosteroids treatment, chloroquine or hydroxychloroquine uptake the last month or any contraindication to hydroxychloroquine treatment. INTERVENTION AND COMPARATOR: Eligible participants will be allocated to one of the two study groups: Intervention group (PrEP): participants will receive the standard of care and will take 400mg of hydroxychloroquine (2 tablets of 200 mg per Dolquine® tablet) daily the first four consecutive days, followed by 400 mg weekly for a period of 6 months. CONTROL GROUP: participants will receive placebo tablets with identical physical appearance to hydroxychloroquine 200 mg (Dolquine®) tablets following the same treatment schedule of the intervention group. Both groups will be encouraged to use the personal protection equipment (PPE) for COVID-19 prevention according to current hospital guidelines. MAIN OUTCOMES: The primary endpoint will be the number of confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative SARS-CoV-2 PCR and serology at day 0. As secondary endpoints, we will obtain: i) the SARS-CoV-2 seroconversion in the PrEP group compared to placebo during the 6 months of follow-up in healthcare workers with negative serology at day 0; ii) the occurrence of any adverse event related with hydroxychloroquine treatment; iii) the incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers in the non-PrEP group, among the total of healthcare workers included in the non-PrEP group during the study period; iv) the risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19; v) a repository of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection. RANDOMISATION: Participants meeting all eligibility requirements will be allocated to one of the two study arms (PrEP with hydroxychloroquine or non-PrEP control group) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Each intervention group will have 220 participants, giving a total of 440 participants. TRIAL STATUS: The current protocol version is 1.5, 2nd of June 2020. Two hundred and seventy-fiveparticipants were recruited and completed first month follow-up until date. The estimated sample size could not be reached yet due to the declining national epidemic curve. Thus, 275 is the total number of participants included until date. The study has been suspended (26th of June) until new epidemic curve occurs. TRIAL REGISTRATION: This trial was registered on April 2nd 2020 at clinicaltrials.gov with the number NCT04331834. 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)
Betacoronavirus , Infecciones por Coronavirus/prevención & control , Personal de Salud , Hidroxicloroquina/uso terapéutico , Pandemias/prevención & control , Neumonía Viral/prevención & control , Profilaxis Pre-Exposición , Ensayos Clínicos Controlados Aleatorios como Asunto , Método Doble Ciego , Humanos , Hidroxicloroquina/efectos adversos
12.
PLoS One ; 15(7): e0236778, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-671516

RESUMEN

BACKGROUND: Severe acute respiratory coronavirus 2 (SARS-CoV-2) has caused a devastating worldwide pandemic. Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2, but clinical data supporting HCQ for coronavirus disease 2019 (COVID-19) are limited. METHODS: This was a retrospective cohort study of hospitalized patients with COVID-19 who received ≥1 dose of HCQ at two New York City hospitals. We measured incident Grade 3 or 4 blood count and liver test abnormalities, ventricular arrhythmias, and vomiting and diarrhea within 10 days after HCQ initiation, and the proportion of patients who completed HCQ therapy. We also describe changes in Sequential Organ Failure Assessment hypoxia scores between baseline and day 10 after HCQ initiation and in-hospital mortality. RESULTS: None of the 153 hospitalized patients with COVID-19 who received HCQ developed a sustained ventricular tachyarrhythmia. Incident blood count and liver test abnormalities occurred in <15% of patients and incident vomiting or diarrhea was rare. Eighty-nine percent of patients completed their HCQ course and three patients discontinued therapy because of QT prolongation. Fifty-two percent of patients had improved hypoxia scores 10 days after starting HCQ. Thirty-one percent of patients who were receiving mechanical ventilation at the time of HCQ initiation died during their hospitalization, compared to 18% of patients who were receiving supplemental oxygen but not requiring mechanical ventilation, and 8% of patients who were not requiring supplemental oxygen. Co-administration of azithromycin was not associated with improved outcomes. CONCLUSIONS: HCQ appears to be reasonably safe and tolerable in most hospitalized patients with COVID-19. However, nearly one-half of patients did not improve with this treatment, highlighting the need to evaluate HCQ and alternate therapies in randomized trials.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Anciano , Azitromicina/uso terapéutico , Betacoronavirus , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Pandemias , Estudios Retrospectivos , Resultado del Tratamiento
13.
Am J Trop Med Hyg ; 103(1): 79-82, 2020 07.
Artículo en Inglés | MEDLINE | ID: covidwho-658335

RESUMEN

Novel coronavirus disease (COVID-19) is a highly contagious disease caused by severe acute respiratory distress syndrome coronavirus-2 that has resulted in the current global pandemic. Currently, there is no available treatment proven to be effective against COVID-19, but multiple medications, including hydroxychloroquine (HCQ), are used off label. We report the case of a 60-year-old woman without any cardiac history who developed right bundle brunch block and critically prolonged corrected electrocardiographic QT interval (QTc 631 ms) after treatment for 3 days with HCQ, which resolved on discontinuation of the medication. This case highlights a significant and potentially life-threatening complication of HCQ use.


Asunto(s)
Bloqueo de Rama/inducido químicamente , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Síndrome de QT Prolongado/inducido químicamente , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Brunei , Ecocardiografía , Femenino , Humanos , Persona de Mediana Edad , Pandemias
14.
Int J Antimicrob Agents ; 56(3): 106101, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-650831

RESUMEN

The coronavirus infection (COVID-19) has turned into a global catastrophe and there is an intense search for effective drug therapy. Of all the potential therapies, chloroquine and hydroxychloroquine have been the focus of tremendous public attention. Both drugs have been used in the treatment and prophylaxis of malaria. Long-term use of hydroxychloroquine is the cornerstone in the treatment of several auto-immune disorders. There is convincing evidence that hydroxychloroquine has strong in vitro antiviral activity against SARS-CoV-2. A few small uncontrolled trials and several anecdotal reports have shown conflicting results of such drug therapy in COVID-19. However, the results of preliminary large-scale randomized controlled trials have failed to show any survival benefit of such drug therapy in COVID-19. Despite the lack of such evidence, hydroxychloroquine has been used as a desperate attempt for prophylaxis and treatment of COVID-19. The drug has wide-ranging drug interactions and potential cardiotoxicity. Indiscriminate unsupervised use can expose the public to serious adverse drug effects.


Asunto(s)
Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/prevención & control , Hidroxicloroquina/administración & dosificación , Factores Inmunológicos/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Antivirales/efectos adversos , Betacoronavirus/efectos de los fármacos , Betacoronavirus/crecimiento & desarrollo , Betacoronavirus/inmunología , Cloroquina/efectos adversos , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/mortalidad , Síndrome de Liberación de Citoquinas/virología , Citocinas/antagonistas & inhibidores , Citocinas/genética , Citocinas/inmunología , Esquema de Medicación , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Hidroxicloroquina/efectos adversos , Factores Inmunológicos/efectos adversos , Pandemias/prevención & control , Neumonía Viral/mortalidad , Neumonía Viral/prevención & control , Neumonía Viral/virología , Análisis de Supervivencia , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
15.
Int J Antimicrob Agents ; 56(1): 106056, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: covidwho-641204

RESUMEN

The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.


Asunto(s)
Azitromicina/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Azitromicina/efectos adversos , Azitromicina/farmacología , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/farmacología , Evaluación de Resultado en la Atención de Salud , Pandemias , Proyectos de Investigación
16.
Neurol Neuroimmunol Neuroinflamm ; 7(5)2020 09.
Artículo en Inglés | MEDLINE | ID: covidwho-638814

RESUMEN

OBJECTIVE: To report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness. METHODS: From March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records. RESULTS: We identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome. CONCLUSIONS: Most patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Esclerosis Múltiple/complicaciones , Neumonía Viral/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/uso terapéutico , Infecciones por Coronavirus/complicaciones , Femenino , Hospitalización , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicaciones , Factores de Riesgo , Factores de Tiempo , Adulto Joven
17.
Trials ; 21(1): 635, 2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: covidwho-640432

RESUMEN

OBJECTIVES: The aim of this trial is to identify the effect of ambulatory treatment in early COVID-19 disease with hydroxychloroquine on the rate of hospitalization or death in older patients above the age of 64. TRIAL DESIGN: Parallel, 2:1 randomization, double blind, placebo-controlled, multi-center trial. PARTICIPANTS: Male and female patients above the age of 64 (i.e. ≥65 years of age) with COVID-19 diagnosis confirmed by SARS-CoV2 positive throat swab (PCR). Patients can only be included within 3 days of symptom onset in ambulatory care if they consent to the study procedure and are able to adhere to the study visit schedule and protocol requirements (including telephone visits concerning symptoms and side effects). Severity of disease at inclusion is mild to moderate defined as not requiring hospital admission: SpO2 >94%, respiratory rate <20, mental state alert, no signs of septic shock. Cardiac risk is minimised by requiring a Tisdale score ≤ 6. Patients are recruited in the two german cities of Ulm and Tübingen in various ambulatory care settings. INTERVENTION AND COMPARATOR: Each patient will be given a first dose of 600 mg Hydroxychloroquine or the equivalent number of placebo capsules (3 capsules) at the day of inclusion. From the 2nd day on, each patient will get 200 mg or the equivalent number of placebo capsules twice a day (400mg/day) until day 7 (6 more does of 400 mg); a cumulative dose of 3 g. MAIN OUTCOMES: Rate of hospitalization or death at day 7 after study inclusion RANDOMISATION: All consenting adult patients having confirmed COVID-19 are randomly and blindly allocated in a 2:1 ratio to either IMP or placebo. The biostatistical center produced a randomization list (block randomization) with varying block length and stratified for the study center. This list is provided for packaging to the pharmaceutical unit which is providing encapsulated placebo and IMP. Only the pharmaceutical unit is aware of group allocation according to the randomization list. BLINDING (MASKING): Patients and investigators, as well as treating physicians are blinded to the treatment- allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the first stage of an adaptive design 120 patients in a 2:1 ration: 72 Verum and 36 Placebo, plus an increase for 10% drop outs. After interim analysis, the total sample size will be calculated based on the effect seen in the first stage. Total sample size is estimated approximately n = 300-400 patients. TRIAL STATUS: Protocol version number: V3, 19.05.2020 Recruitment not yet started but is anticipated to begin by June 2020 and be complete by December 2020 TRIAL REGISTRATION: ClinicalTrials.gov: NCT04351516 , date: 17 April 2020 EudraCT: 2020-001482-37, date: 30 March 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)
Atención Ambulatoria , Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Factores de Edad , Anciano , Envejecimiento , Antivirales/efectos adversos , Betacoronavirus/patogenicidad , Causas de Muerte , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Método Doble Ciego , Esquema de Medicación , Femenino , Alemania , Hospitalización , Interacciones Huésped-Patógeno , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Estudios Multicéntricos como Asunto , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Neumonía Viral/virología , Valor Predictivo de las Pruebas , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
18.
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
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA