Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.012
Filtrar
1.
BMJ Open ; 11(2): e042965, 2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33558355

RESUMEN

OBJECTIVE: To describe the pattern of hydroxychloroquine use and examine the association between hydroxychloroquine use and clinical outcomes arising from changes in the US Food and Drug Administration (FDA)'s recommendation during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: A retrospective cross-sectional analysis. SETTING AND PARTICIPANTS: We included hospitalised adult patients at Northwell Health hospitals with confirmed COVID-19 infections between 1 March 2020 and 11 May 2020. We categorised changes in the FDA's recommendation as pre-FDA approval (1 March 2020-27 March 2020), FDA approval (28 March 2020-23 April 2020), and FDA warning (24 April 2020-11 May 2020). The hydroxychloroquine-treated group received at least one dose within 48 hours of hospital admission. PRIMARY OUTCOME: A composite of intubation and inpatient death. RESULTS: The percentages of patients who were treated with hydroxychloroquine were 192/2202 (8.7%) pre-FDA approval, 2902/6741 (43.0%) FDA approval, and 176/1066 (16.5%) FDA warning period (p<0.001). Using propensity score matching, there was a higher rate of the composite outcome among patients treated with hydroxychloroquine (49/192, 25.5%) compared with no hydroxychloroquine (66/384, 17.2%) in the pre-FDA approval period (p=0.03) but not in the FDA approval period (25.5% vs 22.6%, p=0.08) or the FDA warning (21.0% vs 15.1%, p=0.11) periods. Coincidently, there was an increase in number of patients with COVID-19 and disease severity during the FDA approval period (24.1% during FDA approval vs 21.4% during pre-FDA approval period had the composite outcome). Hydroxychloroquine use was associated with increased odds of the composite outcome during the pre-FDA approval period (OR=1.65 (95% CI 1.09 to 2.51)) but not during the FDA approval (OR=1.17 (95% CI 0.99 to 1.39)) and FDA warning (OR=1.50 (95% CI 0.94 to 2.39)) periods. CONCLUSIONS: Hydroxychloroquine use was associated with adverse clinical outcomes only during the pre-FDA approval period but not during the FDA approval and warning periods, even after adjusting for concurrent changes in the percentage of patients with COVID-19 treated with hydroxychloroquine and the number (and disease severity) of hospitalised patients with COVID-19 infections.


Asunto(s)
/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , United States Food and Drug Administration , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Medicare , Persona de Mediana Edad , New York , Puntaje de Propensión , Estudios Retrospectivos , Estados Unidos , Adulto Joven
2.
Zhonghua Er Ke Za Zhi ; 59(2): 107-112, 2021 Feb 02.
Artículo en Chino | MEDLINE | ID: mdl-33548956

RESUMEN

Objective: To analyze the disease spectrum among children who were using hydroxychloroquine (HCQ), and evaluate the drug's safety and compliance. Methods: From January 2008 to December 2019, children from Children's Hospital of Fudan University who used HCQ were selected as subjects, the disease spectrum of HCQ was analyzed, and the drug safety and compliance were evaluated for the patients who were followed up for more than 6 months. Demographic information, diagnosis, initial dose, time of continuous use, cumulative dosage and related adverse reactions report, project and the results of eye test were collected. Results: A total of 528 cases used HCQ during the 12 years, with 156 male cases and 372 female cases, and age at initial medication was (10.5±3.2) years. Among them, 514 cases (97.3%) had rheumatic disease, 5 had pulmonary interstitial lesions and 9 had other system diseases. The top three of the rheumatic diseases were systemic lupus erythematosus (SLE) in 316 cases (316/514,61.5%), juvenile idiopathic arthritis in 69 cases (69/514,13.4%), and juvenile dermatomyositis in 56 cases (56/514,10.9%). During the same period, 397 cases were diagnosed with SLE, and the utilization rate was 79.6% (316/397), which was the highest compared with other diseases and increased year by year. Pulmonary interstitial lesions included 4 cases with SFTPC gene defect related interstitial lung disease. Of the 528 ceses who were treated with HCQ, 397 cases were included for evaluating HCQ's safety and compliance, the initial dose was (4.2±1.0) mg/kg, duration was 29.6 (14.9, 48.8) months, the longest usage time was 127 months, the largest cumulative dosage was 566.8 g. The continuous usage duration (Z=-3.191, P=0.001) of SLE was significantly higher than those of other diseases, as well as cumulative dosage (Z=-5.355, P=0.001). All cases received comprehensive eye exams before medication, 354 cases (354/397, 89.2%) were followed up in the ophthalmological department, and 65.5% (232/354) of them could be reviewed regularly at least 1 time per year. One case suffered from severe skin adverse reactions when the drug was used for 32.7 months, and no other serious adverse reactions were reported. HCQ related retinopathy was not seen during the follow-up period. There were 5 cases stopped HCQ on their own. Conclusions: HCQ was widely used in rheumatic disease in children, especially in those with SLE. It was safe for long-time usage in children, and the medication compliance and the ophthalmic follow-up was good.


Asunto(s)
Antirreumáticos , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Adolescente , Antirreumáticos/efectos adversos , Niño , Enfermedad Crónica , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Enfermedades Reumáticas/tratamiento farmacológico
3.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462009

RESUMEN

Subretinal fluid accumulation in a patient with systemic lupus erythematosus (SLE) may represent a diagnostic challenge. We present a case of a 43-year-old man with baseline diagnosis of SLE and hydroxychloroquine-associated maculopathy who reported progressive vision loss on the right eye, associated with corticosteroids use for an arthritic crisis. Ophthalmological examination did not reveal any acute finding. On optical coherence tomography, subretinal fluid in the perifoveal area was visible on the right eye, with corresponding enlargement of the visual field defect. An increased choroidal thickness was also visible. Fluorescein angiography revealed, on the right eye, two pinpoint areas of leakage and indocyanine green angiography signs of choroidal vascular hyperpermeability. Considering a diagnosis of a non-central central serous chorioretinopathy, corticosteroids use was interrupted, with resolution of the subretinal fluid. This case illustrates the relevance of a multimodal imaging approach to guide the diagnosis of patient with an SLE with subretinal fluid.


Asunto(s)
Corticoesteroides/efectos adversos , Antirreumáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedades de la Retina/inducido químicamente , Corticoesteroides/uso terapéutico , Adulto , Antirreumáticos/uso terapéutico , Progresión de la Enfermedad , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Masculino , Enfermedades de la Retina/diagnóstico
4.
Rheumatol Int ; 41(2): 257-273, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33386447

RESUMEN

Sudden cardiac death is commonly seen due to arrhythmias, which is a common cardiac manifestation seen in COVID-19 patients, especially those with underlying cardiovascular disease (CVD). Administration of hydroxychloroquine (HCQ) as a potential treatment option during SARS-CoV-2, initially gained popularity, but later, its safe usage became questionable due to its cardiovascular safety, largely stemming from instances of cardiac arrhythmias in COVID-19. Moreover, in the setting of rheumatic diseases, in which patients are usually on HCQ for their primary disease, there is a need to scale the merits and demerits of HCQ usage for the treatment of COVID-19. In this narrative review, we aim to address the association between usage of HCQ and sudden cardiac death in COVID-19 patients. MEDLINE, EMBASE, ClinicalTrials.gov and SCOPUS databases were used to review articles in English ranging from case reports, case series, letter to editors, systematic reviews, narrative reviews, observational studies and randomized control trials. HCQ is a potential cause of sudden cardiac death in COVID-19 patients. As opposed to the reduction in CVD with HCQ in treatment of systemic lupus erythematous, rheumatoid arthritis, and other rheumatic diseases, safe usage of HCQ in COVID-19 patients is unclear; whereby, it is observed to result in QTc prolongation and Torsades de pointes even in patients with no underlying cardiovascular comorbidity. This is occasionally associated with sudden cardiac death or cardiac arrest; hence, its clinical efficacy needs further investigation by large-scale clinical trials.


Asunto(s)
Antirreumáticos/efectos adversos , Muerte Súbita Cardíaca/etiología , Hidroxicloroquina/efectos adversos , Antirreumáticos/administración & dosificación , Humanos , Hidroxicloroquina/administración & dosificación , Pandemias , Enfermedades Reumáticas/tratamiento farmacológico , Medición de Riesgo
5.
Int J Risk Saf Med ; 32(1): 3-17, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33386817

RESUMEN

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario.


Asunto(s)
Antivirales/uso terapéutico , Feto/efectos de los fármacos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Antiinfecciosos/efectos adversos , Antiinfecciosos/uso terapéutico , Antivirales/efectos adversos , Drogas en Investigación , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , India/epidemiología , Uso Fuera de lo Indicado , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/virología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Mujeres Embarazadas , Esteroides/efectos adversos , Esteroides/uso terapéutico
6.
JACC Clin Electrophysiol ; 7(1): 16-25, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33478708

RESUMEN

OBJECTIVES: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM). BACKGROUND: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population. METHODS: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality. RESULTS: Among 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed. CONCLUSIONS: An increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.


Asunto(s)
Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Inhibidores Enzimáticos/efectos adversos , Hidroxicloroquina/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Factores de Edad , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Comorbilidad , Creatinina/sangre , Quimioterapia Combinada , Electrocardiografía , Femenino , Insuficiencia Cardíaca/epidemiología , Hospitalización , Humanos , Síndrome de QT Prolongado/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Troponina I/sangre
7.
PLoS One ; 16(1): e0244778, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33406138

RESUMEN

BACKGROUND: Populations such as healthcare workers (HCW) that are unable to practice physical distancing are at high risk of acquiring Coronavirus disease-2019 (COVID-19). In these cases pharmacological prophylaxis would be a solution to reduce severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) transmission. Hydroxychloroquine has in vitro antiviral properties against SARS CoV-2. We therefore sought to determine the efficacy and safety of hydroxychloroquine as prophylaxis for COVID-19. METHODS AND FINDINGS: We electronically searched EMBASE, MEDLINE, the Cochrane COVID-19 Register of Controlled Trials, Epistemonikos COVID-19, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to September 28th, 2020 for randomized controlled trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes with the corresponding 95% confidence intervals (CIs) using a random-effect model. We identified four RCTs (n = 4921) that met our eligibility criteria. The use of hydroxychloroquine, compared to placebo, did not reduce the risks of developing COVID-19 (RR 0.82, 95% CI 0.65 to 1.04, moderate certainty), hospitalization (RR 0.72, 95% CI 0.34 to 1.50, moderate certainty), or mortality (RR 3.26, 95% CI 0.13 to 79.74, low certainty), however, hydroxychloroquine use increased the risk of adverse events (RR 2.76, 95% CI 1.38 to 5.55, moderate certainty). CONCLUSION: Although pharmacologic prophylaxis is an attractive preventive strategy against COVID-19, the current body of evidence failed to show clinical benefit for prophylactic hydroxychloroquine and showed a higher risk of adverse events when compared to placebo or no prophylaxis.


Asunto(s)
/tratamiento farmacológico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Profilaxis Antibiótica/métodos , Antivirales/uso terapéutico , Humanos , Hidroxicloroquina/metabolismo , Profilaxis Pre-Exposición/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , /patogenicidad
8.
Arq Bras Oftalmol ; 84(1): 2-10, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33470334

RESUMEN

PURPOSE: The aim of the study is to evaluate the retinal and choroidal microvascular changes via optical coherence tomography angiography in patients who received hydroxy-chloroquine. METHODS: In total, 28 eyes of 28 patients (24 females, and 4 males) receiving treatment with hydroxy-chloroquine were assessed in this cross-sectional cohort study (hydroxychloroquine group). The high-and low-risk groups consisted of patients receiving hydroxychloroquine for ≥5 years (14 eyes of 28 patients) and <5 years (14 eyes of 28 patients), respectively. A total of 28 age- and gender-matched volunteers were enrolled as the control group. The macular flow area (superficial, deep, and choriocapillaris), superficial and deep vessel density, foveal avascular zone area, central foveal thickness, and subfoveal choroidal thickness parameters were measured by optical coherence tomography angiography. RESULTS: The mean age of the 28 patients who received hydroxychloroquine and the 28 age-matched controls was 45.5 ± 11.1 years (range: 29-70 years) and 44.5 ± 13.9 years (range: 28-70 years), respectively. In patients who received hydroxychloroquine, the values for the superficial, deep, and choriocapillaris macular flow areas were 13.578 ± 0.30, 13.196 ± 0.31, and 17.617 ± 0.42, respectively. In controls, these values were 16.407 ± 0.95, 13.857 ± 0.31, and 18.975 ± 0.76, respectively (p<0.05 for all). The superficial, deep, and cho-riocapillaris flow areas were significantly smaller in patients who received hydroxychloroquine than those in controls (p<0.05 for all). Superficial and deep vessel densities were significantly reduced in patients who received hydroxychlo-roquine in all regions (i.e., foveal, parafoveal, temporal, superior, nasal, and inferior) (p<0.05 for all). Moreover, significant difference was observed between the groups in the foveal avascular zone area (superficial and deep), central foveal thickness, and subfoveal choroidal thickness (p<0.05 for all). CONCLUSIONS: Retinochoroidal microvascular flow and vessel density of the macular area were significantly decreased in patients who received hydroxychloroquine. Hy-droxychloroquine may damage the retinochoroidal mi-cro-vascular architecture. Optical coherence tomography angiography may contribute to the early detection of hy-dro-xychloroquine-induced retinal toxicity.


Asunto(s)
Hidroxicloroquina , Tomografía de Coherencia Óptica , Adulto , Anciano , Coroides/diagnóstico por imagen , Estudios Transversales , Femenino , Angiografía con Fluoresceína , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , Vasos Retinianos/diagnóstico por imagen , Agudeza Visual
9.
Trials ; 22(1): 4, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397429

RESUMEN

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.


Asunto(s)
Antivirales/administración & dosificación , Ivermectina/administración & dosificación , /aislamiento & purificación , Administración Oral , Adulto , Antivirales/efectos adversos , /virología , Ensayos Clínicos Fase III como Asunto , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Interferón beta-1a/administración & dosificación , Interferón beta-1a/efectos adversos , Irán , Ivermectina/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad
10.
Rev Med Suisse ; 17(720-1): 80-84, 2021 Jan 13.
Artículo en Francés | MEDLINE | ID: mdl-33443836

RESUMEN

The main pharmacovigilance updates in 2020 are reviewed. Remdesivir in COVID-19: relatively safe but turns out to be less effective than expected. Hydroxychloroquine in COVID-19 : lack of efficacy and risk of arrhythmias. Cytokines storm in COVID-19: may impact pharmacokinetics. VEGF inhibitors: risk of aneurysm and artery dissection. Tofacitinib: dose-dependant risk of venous thromboembolic events. Ondansetron in the first trimester of pregnancy : a highly debated risk of orofacial cleft defects. Fingolimod : contraindicated during pregnancy due to suspected risk of congenital malformations. Ranitidine: global market withdrawal due to contamination with nitrosamines. Ulipristal for uterine fibroids : market withdrawal due to risk of severe liver injury. Ingenol mebutate : market withdrawal due to paradoxical risk of skin cancers.


Asunto(s)
Farmacovigilancia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Labio Leporino/prevención & control , Contraindicaciones de los Medicamentos , Síndrome de Liberación de Citoquinas/virología , Femenino , Clorhidrato de Fingolimod/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Leiomioma/tratamiento farmacológico , Norpregnadienos/uso terapéutico , Farmacocinética , Embarazo , Ranitidina/efectos adversos , Retirada de Medicamento por Seguridad , Neoplasias Cutáneas/inducido químicamente
11.
Am J Emerg Med ; 40: 41-46, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33348222

RESUMEN

PURPOSE: We investigated the efficacy and safety of hydroxychloroquine for empirical treatment of outpatients with confirmed COVID-19. METHODS: In this prospective, single-center study, we enrolled ambulatory outpatients with COVID-19 confirmed by a molecular method who received hydroxychloroquine. The patients were divided into low- and moderate-risk groups based on the Tisdale risk score for drug-associated QT prolongation, and the QT interval was corrected for heart rate using the Bazett formula (QTc). The QTc interval was measured by electrocardiography both pretreatment (QTc1) and 4 h after the administration of hydroxychloroquine (QTc2). The difference between the QTc1 and QTc2 intervals was defined as the ΔQTc. The QTc1 and QTc2 intervals and ΔQTc values were compared between the two risk groups. RESULTS: The median and interquartile range (IQR) age of the patients was 47.0 (36.2-62) years, and there were 78 men and 74 women. The median (IQR) QTc1 interval lengthened from 425.0 (407.2-425.0) to 430.0 (QTc2; 412.0-443.0) milliseconds (ms). However, this was not considered an increased risk of ventricular tachycardia associated with a prolonged QTc interval requiring drug discontinuation, because none of the patients had a ΔQTc of >60 ms or a QTc2 of >500 ms. Moreover, the median (quartiles; minimum-maximum) ΔQTc value was higher in patients in the moderate-risk group than those in the low-risk group (10.0 [-4.0-18.0; -75.0-51.0] vs. 7.0 [-10.5-23.5; -53.0-59.0 ms]) (p = 0.996). Clinical improvement was noted in 91.4% of the patients, the exceptions being 13 patients who presented with non-serious adverse drug reactions or who had severe COVID-19 and were hospitalized. Adverse effects related to hydroxychloroquine were non-serious and occurred in 52.8% (n = 80) of the patients. CONCLUSIONS: Our findings show that hydroxychloroquine is safe for COVID-19 and not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation. Additionally, hydroxychloroquine was well tolerated, and there were no drug-related non-serious adverse events leading to treatment discontinuation in the majority of patients who were stable and did not require hospitalization.


Asunto(s)
/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Adulto , Atención Ambulatoria , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento
12.
Redox Biol ; 38: 101810, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33360293

RESUMEN

The recent global pandemic due to COVID-19 is caused by a type of coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite rigorous efforts worldwide to control the spread and human to human transmission of this virus, incidence and death due to COVID-19 continue to rise. Several drugs have been tested for treatment of COVID-19, including hydroxychloroquine. While a number of studies have shown that hydroxychloroquine can prolong QT interval, potentially increasing risk of ventricular arrhythmias and Torsade de Pointes, its effects on immune cell function have not been extensively examined. In the current review, an overview of coronaviruses, viral entry and pathogenicity, immunity upon coronavirus infection, and current therapy options for COVID-19 are briefly discussed. Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged/oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs. Therefore, it is likely that hydroxychloroquine treatment may in fact impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with co-morbidities. Further, this review provides a rationale for developing and selecting antiviral drugs and includes a brief review of traditional strategies combined with new drugs to combat COVID-19.


Asunto(s)
Presentación de Antígeno/efectos de los fármacos , Antivirales , Muerte Celular Autofágica , Hidroxicloroquina , Pandemias , /inmunología , Antivirales/efectos adversos , Antivirales/uso terapéutico , Muerte Celular Autofágica/efectos de los fármacos , Muerte Celular Autofágica/inmunología , /epidemiología , /patología , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Oxidación-Reducción/efectos de los fármacos
14.
Eur J Pharmacol ; 893: 173813, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33345848

RESUMEN

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an enormous challenge to the medical system, especially the lack of safe and effective COVID-19 treatment methods, forcing people to look for drugs that may have therapeutic effects as soon as possible. Some old drugs have shown clinical benefits after a few small clinical trials that attracted great attention. Clinically, however, many drugs, including those currently used in COVID-19, such as chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir, may cause cardiotoxicity by acting on cardiac potassium channels, especially hERG channel through their off-target effects. The blocking of the hERG channel prolongs QT intervals on electrocardiograms; thus, it might induce severe ventricular arrhythmias and even sudden cardiac death. Therefore, while focusing on the efficacy of COVID-19 drugs, the fact that they block hERG channels to cause arrhythmias cannot be ignored. To develop safer and more effective drugs, it is necessary to understand the interactions between drugs and the hERG channel and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of drug-related blockade of the hERG channel to provide insights into QT prolongation caused by off-label use of related drugs in COVID-19, and hope to weigh the risks and benefits when using these drugs.


Asunto(s)
Azitromicina/efectos adversos , Azitromicina/uso terapéutico , /tratamiento farmacológico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Canal de Potasio ERG1/efectos de los fármacos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Síndrome de QT Prolongado/inducido químicamente , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Combinación de Medicamentos , Humanos , Síndrome de QT Prolongado/epidemiología , Uso Fuera de lo Indicado
15.
Int J Infect Dis ; 103: 599-606, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33316389

RESUMEN

BACKGROUND & AIMS: Hydroxychloroquine (HCQ) and chloroquine (CQ) are anti-malarial drugs frequently used in the rheumatologic field. They were recently identified as potential therapeutic options for Coronavirus Disease (COVID-19). The present study aims to map and grade the diverse health outcomes associated with HCQ/CQ using an umbrella review approach. METHODS: Umbrella review of systematic reviews of observational and intervention studies. For observational studies, random-effects summary effect size, 95% confidence interval, and 95% prediction interval were estimated. We also assessed heterogeneity, evidence for small-study effect, and evidence for excess significance bias. The quality of evidence was then graded using validated criteria from highly convincing to weak. The evidence from randomized controlled trials (RCTs) was graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. RESULTS: From 313 articles returned in the literature search, six meta-analyses were included (n = 25 outcomes). Among meta-analyses (MAs) of observational studies, HCQ/CQ are weakly associated with a reduced risk for cardiovascular events and diabetes when used for autoimmune diseases and with spontaneous abortion; they are also associated with a higher risk of death in COVID-19 patients. Among MAs of RCTs, HCQ/CQ are associated with an improvement of articular manifestations of rheumatic diseases. CONCLUSIONS: There is high evidence of the efficacy of HCQ/CQ in the rheumatologic field. The lack of evidence for efficacy and the risk of death associated with the use of HCQ/CQ for COVID-19 indicate the inappropriateness of their inclusion in recent COVID-19 therapy guidelines and the urgent need for RCTs to determine eventual appropriateness as a COVID-19 therapy.


Asunto(s)
/tratamiento farmacológico , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Cloroquina/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos
17.
J Antimicrob Chemother ; 76(1): 30-42, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33031488

RESUMEN

OBJECTIVES: Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. METHODS: We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. RESULTS: Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00-1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. CONCLUSIONS: Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Azitromicina/uso terapéutico , Cloroquina/efectos adversos , Hospitalización/estadística & datos numéricos , Humanos , Hidroxicloroquina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
18.
Artículo en Inglés | IBECS | ID: ibc-196946

RESUMEN

OBJECTIVES: To assess the efficacy and safety of hydroxychloroquine (HCQ) compared with no treatment in healthcare workers with mild SARS-CoV-2 infection. METHODS: Prospective, non-randomized study. All health professionals with confirmed COVID-19 between April 7 and May 6, 2020, non-requiring initial hospitalization were asked to participate. Patients who accepted treatment were given HCQ for five days (loading dose of 400 mg q12 h the first day followed by 200 mg q12 h). Control group included patients with contraindications for HCQ or who rejected treatment. Study outcomes were negative conversion and viral dynamics of SARS-CoV-2, symptoms duration and disease progression. RESULT: Overall, 142 patients were enrolled: 87 in treatment group and 55 in control group. The median age was 37 years and 75% were female, with few comorbidities. There were no significant differences in time to negative conversion of PCR between both groups. The only significant difference in the probability of negative conversion of PCR was observed at day 21 (18.7%, 95%CI 2.0-35.4). The decrease of SARS-CoV-2 viral load during follow-up was similar in both groups. A non significant reduction in duration of some symptoms in HCQ group was observed. Two patients with HCQ and 4 without treatment developed pneumonia. No patients required admission to the Intensive Care Unit or died. About 50% of patients presented mild side effects of HCQ, mainly diarrhea. CONCLUSIONS: Our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms in health care workers with mild COVID-19


OBJETIVOS: Evaluar la eficacia y seguridad de hidroxicloroquina (HCQ), en comparación con la ausencia de tratamiento en los profesionales sanitarios con infección leve por SARS-CoV-2. MÉTODOS: Estudio prospectivo y no aleatorio. Se solicitó su participación a todos los profesionales sanitarios con diagnóstico confirmado de COVID-19, entre el 7 de abril y el 6 de mayo de 2020, que no requirieron hospitalización inicial. Los pacientes que aceptaron el tratamiento recibieron HCQ durante cinco días (dosis de carga de 400 mg cada 12 h el primer día, y a continuación 200 mg cada 12 h). El grupo control incluyó pacientes con contraindicaciones de HCQ, o que rechazaron el tratamiento. Los resultados del estudio fueron conversión negativa y dinámica viral de SARS-CoV-2, duración de los síntomas y progresión de la enfermedad. RESULTADOS: En total se incluyeron 142 pacientes: 87 en el grupo de tratamiento, y 55 en el grupo control. La edad media fue de 37 años, y el 75% fueron mujeres, con pocas comorbilidades. No existieron diferencias significativas en cuanto al tiempo transcurrido hasta la conversión negativa de la PCR entre ambos grupos. La única diferencia significativa en cuanto a la probabilidad de negativización de la PCR se observó el día 21 (18,7%, IC 95% 2-35,4). El descenso de la carga viral de SARS-CoV-2 durante el seguimiento fue similar en ambos grupos. Se observó una reducción no significativa de la duración de algunos síntomas en el grupo HCQ. Dos pacientes con HCQ y cuatro sin tratamiento desarrollaron neumonía. Ningún paciente requirió ingreso en la Unidad de Cuidados Intensivos, ni hubo fallecidos. Cerca del 50% de los pacientes presentó efectos secundarios leves de HCQ, principalmente diarrea. CONCLUSIONES: Nuestro estudio no reflejó un beneficio sustancial de HCQ, en cuanto a dinámica viral y resolución de los síntomas clínicos en los profesionales sanitarios con infección leve por COVID-19


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Pandemias , Hidroxicloroquina/uso terapéutico , Personal de Salud , Hidroxicloroquina/efectos adversos , Resultado del Tratamiento , Estudios de Seguimiento
19.
Swiss Med Wkly ; 150: w20446, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33382449

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , /epidemiología , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Antivirales/efectos adversos , Niño , Preescolar , Comorbilidad , Combinación de Medicamentos , Quimioterapia Combinada , Gastos en Salud , Mortalidad Hospitalaria/tendencias , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Lactante , Tiempo de Internación/estadística & datos numéricos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores Socioeconómicos , Terapias en Investigación/métodos , Adulto Joven
20.
Intern Med J ; 50(12): 1559-1562, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33354884

RESUMEN

Hydroxychloroquine is being used for COVID-19 symptoms and in clinical trials, but can cause a toxic myopathy that leads to muscle weakness. A review of skeletal muscle biopsies from patients with hydroxychloroquine myopathy gives pointers of steps that can be taken to diagnose this toxic myopathy early and help differentiate it from COVID-19-related muscle weakness.


Asunto(s)
/diagnóstico , Hidroxicloroquina/efectos adversos , Debilidad Muscular/inducido químicamente , Debilidad Muscular/diagnóstico , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Diagnóstico Diferencial , Humanos , Hidroxicloroquina/administración & dosificación , Persona de Mediana Edad , Pandemias
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA