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1.
Cir Cir ; 88(5): 569-575, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064694

RESUMO

Objective: To describe the clinical characteristics and management of severe COVID-19 patients. Method: Observational, descriptive, longitudinal, and retrospective study. Results: 56 patients were admitted, of whom 80.3% (n = 45) were males with a mean age of 58 years [46-67]. The main comorbidities were obesity, high blood pressure, and diabetes. Symptoms onset time at admittance to the ICU was 9 [7-14] days, of which the most frequent were dyspnea, fever, and dry cough. Laboratory data were lymphopenia; elevation of LDH, fibrinogen, D-dimer, ferritin and CRP. 100% of the patients required mechanical ventilation, the median mechanical ventilation time was 12 [6-17] days, and 66% (n= 37) required a prone position. The pharmacological treatment was mainly based on azithromycin, hydroxychloroquine, tocilizumab and steroids. The most frequent complications were acute kidney injury, venous thromboembolism and acute myocardial infarction. Mortality rate was 17.8% (n = 10). Conclusion: The characteristics of the critically ill patients in our hospital were mostly elderly and obese, with the variables of higher SOFA score and acute kidney injury associated with higher mortality.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/terapia , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Corticosteroides/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Terapia Combinada , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Feminino , Mortalidade Hospitalar , Hospitais Universitários/organização & administração , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Respiração Artificial , Avaliação de Sintomas
2.
PLoS Med ; 17(9): e1003285, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931496

RESUMO

BACKGROUND: Biannual azithromycin distribution has been shown to reduce child mortality as well as increase antimicrobial resistance. Targeting distributions to vulnerable subgroups such as malnourished children is one approach to reaching those at the highest risk of mortality while limiting selection for resistance. The objective of this analysis was to assess whether the effect of azithromycin on mortality differs by nutritional status. METHODS AND FINDINGS: A large simple trial randomized communities in Niger to receive biannual distributions of azithromycin or placebo to children 1-59 months old over a 2-year timeframe. In exploratory subgroup analyses, the effect of azithromycin distribution on child mortality was assessed for underweight subgroups using weight-for-age Z-score (WAZ) thresholds of -2 and -3. Modification of the effect of azithromycin on mortality by underweight status was examined on the additive and multiplicative scale. Between December 2014 and August 2017, 27,222 children 1-11 months of age from 593 communities had weight measured at their first study visit. Overall, the average age among included children was 4.7 months (interquartile range [IQR] 3-6), 49.5% were female, 23% had a WAZ < -2, and 10% had a WAZ < -3. This analysis included 523 deaths in communities assigned to azithromycin and 661 deaths in communities assigned to placebo. The mortality rate was lower in communities assigned to azithromycin than placebo overall, with larger reductions among children with lower WAZ: -12.6 deaths per 1,000 person-years (95% CI -18.5 to -6.9, P < 0.001) overall, -17.0 (95% CI -28.0 to -7.0, P = 0.001) among children with WAZ < -2, and -25.6 (95% CI -42.6 to -9.6, P = 0.003) among children with WAZ < -3. No statistically significant evidence of effect modification was demonstrated by WAZ subgroup on either the additive or multiplicative scale (WAZ < -2, additive: 95% CI -6.4 to 16.8, P = 0.34; WAZ < -2, multiplicative: 95% CI 0.8 to 1.4, P = 0.50, WAZ < -3, additive: 95% CI -2.2 to 31.1, P = 0.14; WAZ < -3, multiplicative: 95% CI 0.9 to 1.7, P = 0.26). The estimated number of deaths averted with azithromycin was 388 (95% CI 214 to 574) overall, 116 (95% CI 48 to 192) among children with WAZ < -2, and 76 (95% CI 27 to 127) among children with WAZ < -3. Limitations include the availability of a single weight measurement on only the youngest children and the lack of power to detect small effect sizes with this rare outcome. Despite the trial's large size, formal tests for effect modification did not reach statistical significance at the 95% confidence level. CONCLUSIONS: Although mortality rates were higher in the underweight subgroups, this study was unable to demonstrate that nutritional status modified the effect of biannual azithromycin distribution on mortality. Even if the effect were greater among underweight children, a nontargeted intervention would result in the greatest absolute number of deaths averted. TRIAL REGISTRATION: The MORDOR trial is registered at clinicaltrials.gov NCT02047981.


Assuntos
Azitromicina/uso terapêutico , Transtornos da Nutrição Infantil/tratamento farmacológico , Transtornos da Nutrição Infantil/mortalidade , Antibacterianos/uso terapêutico , Peso Corporal , Mortalidade da Criança/tendências , Pré-Escolar , Feminino , Humanos , Lactente , Mortalidade Infantil/tendências , Malária/tratamento farmacológico , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/mortalidade , Níger/epidemiologia , Estado Nutricional , Magreza
3.
Lancet ; 396(10256): 959-967, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-32896292

RESUMO

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus , Brasil/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Terapia Respiratória , Padrão de Cuidado , Resultado do Tratamento
4.
PLoS One ; 15(9): e0238681, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881982

RESUMO

BACKGROUND: The rapid spread of the disease caused by the novel SARS-CoV-2 virus has led to the use of multiple therapeutic agents whose efficacy has not been previously demonstrated. The objective of this study was to analyze whether there is an association between the use of azithromycin and the evolution of the pulmonary disease or the time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI ratio (oxygen saturation/fraction of inspired oxygen) in the first 48 hours of treatment and the time to discharge. The results were compared between patients treated and untreated with the study drug through subcohort analyses matched for multiple clinical and prognostic factors, as well as through analysis of non-matched subcohorts, using Cox multivariate models adjusted for prognostic factors. RESULTS: There were 239 patients treated with azithromycin. Of these, 29 patients treated with azithromycin could be matched with an equivalent number of control patients. In the analysis of these matched subcohorts, SAFI at 48h had no significant changes associated to the use of azithromycin, though azithromycin treatment was associated with a longer time to discharge (10.0 days vs 6.7 days; log rank: p = 0.039). However, in the unmatched cohorts, the increased hospital stay associated to azithromycin use, was no significant after adjustment using Multivariate Cox regression models: hazard ratio 1.45 (IC95%: 0.88-2.41; p = 0.150). This study is limited by its small sample size and its observational nature; despite the strong pairing of the matched subcohorts and the adjustment of the Cox regression for multiple factors, the results may be affected by residual confusion. CONCLUSIONS: We did not find a clinical benefit associated with the use of azithromycin, in terms of lung function 48 hours after treatment or length of hospital stay.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Idoso , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente/estatística & dados numéricos
5.
JAMA Cardiol ; 5(9): 1036-1041, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936252

RESUMO

Importance: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. Conclusions and Relevance: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/epidemiologia , Pneumonia Viral/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Medição de Risco
9.
BMJ Open ; 10(9): e041276, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32948577

RESUMO

OBJECTIVES: To characterise current COVID-19-related research activities. DESIGN: Cross-sectional analysis. SETTING: Clinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19. DATA SOURCES: ClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic. MAIN OUTCOME MEASURES: We classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date. RESULTS: Of the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020. CONCLUSIONS: These findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates.


Assuntos
Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Sistema de Registros , Transplante de Células-Tronco , Anticorpos Monoclonais Humanizados/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Método Duplo-Cego , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Lopinavir/uso terapêutico , Pandemias , Ritonavir/uso terapêutico , Método Simples-Cego
10.
Trends Immunol ; 41(10): 856-859, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32863134

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mainly affects the lungs. Sarcoidosis is an autoinflammatory disease characterized by the diffusion of granulomas in the lungs and other organs. Here, we discuss how the two diseases might involve some common mechanistic cellular pathways around the regulation of autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Edema Pulmonar/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Autofagia/genética , Azitromicina/uso terapêutico , Betacoronavirus/crescimento & desenvolvimento , Cloroquina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Isoniazida/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/virologia , Edema Pulmonar/epidemiologia , Edema Pulmonar/genética , Edema Pulmonar/virologia , Rifampina/uso terapêutico , Sarcoidose/epidemiologia , Sarcoidose/genética , Sarcoidose/virologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença
11.
Int J Antimicrob Agents ; 56(4): 106129, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32755653

RESUMO

INTRODUCTION: The effect of anti-infective agents in COVID-19 is unclear. The impact of changes in practice on prognosis over time has not been evaluated. METHODS: Single center, retrospective study in adults hospitalized in a medicine ward for COVID-19 from March 5th to April 25th 2020. Patient characteristics were compared between two periods (before/after March 19th) considering French guidelines. The aim of the study was to evaluate how medical care impacted unfavorable outcome, namely admission to intensive care unit (ICU) and/or death. RESULTS: A total of 132 patients were admitted: mean age 59.0±16.3 years; mean C-reactive protein (CRP) level 84.0±71.1 mg/L; 46% had a lymphocyte count <1000/mm3. Prescribed anti-infective agents were lopinavir-ritonavir (n=12), azithromycin (AZI) (n=28) and AZI combined with hydroxychloroquine (HCQ) (n=52). There was a significant decrease in ICU admission, from 43% to 12%, between the two periods (P<0.0001). Delays until transfer to ICU were similar between periods (P=0.86). Pulmonary computerized tomography (CT)-scans were performed significantly more often with time (from 50% to 90%, P<0.0001), and oxygen-dependency (53% vs 80%, P=0.001) and prescription of AZI±HCQ (from 25% to 76%, P<0.0001) were also greater over time. Multivariate analyses showed a reduction of unfavorable outcome in patients receiving AZI±HCQ (hazard ratio [HR]=0.45, 95% confidence interval [CI: 0.21-0.97], P=0.04), particularly among an identified category of individuals (lymphocyte ≥1000/mm3 or CRP ≥100 mg/L). CONCLUSION: The present study showed a significant decrease in admission to ICU over time, which was probably related to multiple factors, including a better indication of pulmonary CT-scan, oxygen therapy, and a suitable prescription of anti-infective agents.


Assuntos
Anti-Infecciosos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Idoso , Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Progressão da Doença , Combinação de Medicamentos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Linfócitos T/patologia , Linfócitos T/virologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Respiration ; 99(8): 667-677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756065

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. OBJECTIVE: We explored the clinical management of inpatients with COVID-19 in Italy. METHODS: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. RESULTS: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. CONCLUSIONS: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.


Assuntos
Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Hospitalização , Pneumonia Viral/terapia , Padrões de Prática Médica , Inibidores de Proteases/uso terapêutico , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Cânula , Cardiologia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Cuidados Críticos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , Medicina Interna , Itália , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Ventilação não Invasiva/métodos , Pandemias , Médicos , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumologia , Encaminhamento e Consulta , Insuficiência Respiratória/etiologia , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
13.
Int J Antimicrob Agents ; 56(4): 106143, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853672

RESUMO

As no specific pharmacological treatment has been validated for use in coronavirus disease 2019 (COVID-19), we aimed to assess the effectiveness of azithromycin (AZM) in these patients at a referral centre in Iran. An open-label, randomised controlled trial was conducted on patients with laboratory-confirmed COVID-19. A total of 55 patients in the control group receiving hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) were compared with 56 patients in the case group who in addition to the same regimen also received AZM. Patients with prior cardiac disease were excluded from the study. Furthermore, patients from the case group were assessed for cardiac arrythmia risk based on the American College of Cardiology (ACC) risk assessment for use of AZM and HCQ. The main outcome measures were vital signs, SpO2 levels, duration of hospitalisation, need for and length of intensive care unit admission, mortality rate and results of 30-day follow-up after discharge. Initially, there was no significant difference between the general conditions and vital signs of the two groups. The SpO2 levels at discharge were significantly higher, the respiratory rate was lower and the duration of admission was shorter in the case group. There was no significant difference in the mortality rate between the two groups. Patients who received AZM in addition to HCQ and LPV/r had a better general condition. HCQ+AZM combination may be beneficial for individuals who are known to have a very low underlying risk for cardiac arrhythmia based on the ACC criteria.


Assuntos
Anti-Infecciosos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Idoso , Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Progressão da Doença , Combinação de Medicamentos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Prognóstico , Testes de Função Respiratória , Análise de Sobrevida , Linfócitos T/patologia , Linfócitos T/virologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Nephrol Dial Transplant ; 35(8): 1346-1353, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32844224

RESUMO

BACKGROUND: Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients. METHODS: We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns. RESULTS: Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1-1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days). CONCLUSIONS: HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Tolerância a Medicamentos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/terapia , Pneumonia Viral/tratamento farmacológico , Diálise Renal/métodos , Idoso , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Comorbidade , Infecções por Coronavirus/epidemiologia , Feminino , França/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pandemias , Pneumonia Viral/epidemiologia
15.
Brasília; s.n; 7 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117973

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 12 artigos e 4 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Sistema Renina-Angiotensina , Avaliação da Tecnologia Biomédica , Dexametasona/uso terapêutico , Vacinas/uso terapêutico , Cloroquina/uso terapêutico , Interferons/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Rituximab/uso terapêutico , Hidroxicloroquina/uso terapêutico
16.
Brasília; s.n; 11 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117979

RESUMO

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


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Ácido Ursodesoxicólico/uso terapêutico , Imunoglobulinas/uso terapêutico , Prednisolona/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Cloroquina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interferon-alfa/uso terapêutico , Tacrolimo/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Células-Tronco Mesenquimais , Lopinavir/uso terapêutico , Ácido Fólico/uso terapêutico , Meropeném/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Ácido Micofenólico/uso terapêutico
17.
Brasília; s.n; 12 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117983

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 10 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Ivermectina/uso terapêutico , Imunoglobulinas/uso terapêutico , Vacina BCG/uso terapêutico , Colchicina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Lopinavir/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Telmisartan/uso terapêutico , Hidroxicloroquina/uso terapêutico
18.
Trials ; 21(1): 718, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807209

RESUMO

BACKGROUND: Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin's antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule's anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1ß, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease. METHODS: ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers. DISCUSSION: This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide. TRIAL REGISTRATION: ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Pandemias , Estudos Prospectivos , Projetos de Pesquisa , Índice de Gravidade de Doença
19.
Trials ; 21(1): 702, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32771032

RESUMO

OBJECTIVES: To evaluate the effectiveness of Hydroxychloroquine Phosphate/Sulfate (200 mg orally 8 hourly thrice a day for 5 days), versus oseltamivir (75 mg orally twice a day for 5 days), and versus Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus (COVID-19) nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes). TRIAL DESIGN: An adaptive design, set within a comprehensive cohort study, to permit flexibility in this fast-changing clinical and public health scenario. The randomized study will be a multicenter, multiarm, multistage, randomized controlled trial with a parallel design. An observation only cohort will emerge from those not consenting to randomization. PARTICIPANTS: Eligible will be newly diagnosed patients, either hospitalized or in self-isolation, without any comorbidities or with controlled chronic medical conditions like diabetes mellitus and hypertension. Participants of any gender or age group having tested positive for COVID-19 on Real-Time qRT-PCR (Quantitative Reverse Transcription PCR) will be invited to take part in study at twelve centers across eight cities in Pakistan. Those pregnant or lactating, severely dyspneic or with respiratory distress, already undergoing treatment, and with serious comorbidities like liver or kidney failure will be excluded. INTERVENTION AND COMPARATOR: There will be a total of seven comparator groups: Each drug (Hydroxychloroquine Phosphate/Sulfate, Oseltamivir and Azithromycin) given as monotherapy (three groups); combinations of each of two drugs (three groups); and a final group on triple drug regimen. MAIN OUTCOMES: The laboratory-based primary outcome will be turning the test negative for COVID-19 on qRT-PCR on day 7 of follow-up. The clinical primary outcome will be improvement from baseline of two points on a seven-category ordinal scale of clinical status on day 7 of follow-up. RANDOMIZATION: Participants will be randomized, maintaining concealment of allocation sequence, using a computer-generated random number list of variable block size into multiple intervention groups in the allocation ratio of 1:1 for all groups. BLINDING (MASKING): This is an open label study, neither physician nor participants will be blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is an adaptive design and parameters for formal sample size calculation in a new disease of a previously unknown virus are not available. Thus, the final sample size will be subjected to periodic reviews at each stage of adaptive design and subsequent advice of National Data Safety & Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan. TRIAL STATUS: Protocol Version 1.7 dated July 5, 2020. By July 03, 2020, the trial had recruited a total of about 470 participants across 12 centers after approval from the National Bioethics Committee and Drug Regulatory Authority of Pakistan. Recruitment started on April 20, 2020. The recruitment is expected to continue for at least three months subject to review by the National Data Safety and Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan. TRIAL REGISTRATION: Prospectively registered on 8 April 2020 at clinicaltrials.gov ID: NCT04338698 The full protocol is attached as an additional file, accessible from the Trials website (Additional file1). 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file2).


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Oseltamivir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Comorbidade , Humanos , Pandemias , Projetos de Pesquisa
20.
Rheumatol Int ; 40(10): 1593-1598, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32794113

RESUMO

OBJECTIVE: To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization. METHODS: We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization. RESULTS: A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization. CONCLUSION: Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Glucocorticoides/uso terapêutico , Hospitalização/estatística & dados numéricos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Idoso , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Azitromicina/uso terapêutico , Betacoronavirus , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Modelos Logísticos , Lopinavir/uso terapêutico , Pneumopatias/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Estudos Retrospectivos , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Fatores Sexuais , Espanha/epidemiologia
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