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2.
PLoS One ; 15(10): e0239389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33057434

RESUMO

INTRODUCTION: The COVID-19 pandemic has posed major challenges to all aspects of healthcare. Malta's population density, large proportion of elderly and high prevalence of diabetes and obesity put the country at risk of uncontrolled viral transmission and high mortality. Despite this, Malta achieved low mortality rates compared to figures overseas. The aim of this paper is to identify key factors that contributed to these favorable outcomes. METHODS: This is a retrospective, observational, nationwide study which evaluates outcomes of patients during the first wave of the pandemic in Malta, from the 7th of March to the 24th of April 2020. Data was collected on demographics and mode of transmission. Hospitalization rates to Malta's main general hospital, Mater Dei Hospital, length of in-hospital stay, intensive care unit admissions and 30-day mortality were also analyzed. RESULTS: There were 447 confirmed cases in total; 19.5% imported, 74.2% related to community transmission and 6.3% nosocomially transmitted. Ninety-three patients (20.8%) were hospitalized, of which 4 were children. Patients with moderate-severe disease received hydroxychloroquine and azithromycin, in line with evidence available at the time. A total of 4 deaths were recorded, resulting in an all-cause mortality of 0.89%. Importantly, all admitted patients with moderate-severe disease survived to 30-day follow up. CONCLUSION: Effective public health interventions, widespread testing, remote surveillance of patients in the community and a low threshold for admission are likely to have contributed to these favorable outcomes. Hospital infection control measures were key in preventing significant nosocomial spread. These concepts can potentially be applied to stem future outbreaks of viral diseases. Patients with moderate-severe disease had excellent outcomes with no deaths reported at 30-day follow up.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Uso de Medicamentos/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Malta , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Análise de Sobrevida
3.
Klin Onkol ; 33(5): 386-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108884

RESUMO

BACKGROUND: In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection. CASE: In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease. RESULTS: On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG. CONCLUSION: An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.


Assuntos
Adenocarcinoma/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Neoplasias Gástricas/complicações , Idoso , Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/administração & dosagem , Masculino , Pandemias , Alta do Paciente , Pneumonia Viral/tratamento farmacológico , Eslováquia , Resultado do Tratamento
4.
Med. clín (Ed. impr.) ; 155(5): 202-204, sept. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188495

RESUMO

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


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


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/mortalidade , Neoplasias/epidemiologia , Comorbidade , Neoplasias/complicações , Febre/complicações , Tosse/complicações , Dispneia/complicações , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Azitromicina/administração & dosagem , Antineoplásicos/administração & dosagem , Unidades de Terapia Intensiva/estatística & dados numéricos
7.
Toxicol Appl Pharmacol ; 406: 115237, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920000

RESUMO

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


Assuntos
Betacoronavirus , Simulação por Computador , Mineração de Dados/métodos , Toxicogenética/métodos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Bases de Dados Genéticas , Quimioterapia Combinada , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
8.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871902

RESUMO

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


Assuntos
Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus , Exantema , Glucocorticoides/administração & dosagem , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pandemias , Pneumonia Viral , Ritonavir/administração & dosagem , Administração Tópica , Adulto , Antivirais/administração & dosagem , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Exantema/diagnóstico , Exantema/tratamento farmacológico , Exantema/etiologia , Exantema/imunologia , Feminino , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Avaliação de Sintomas/métodos , Resultado do Tratamento
9.
J Cardiovasc Med (Hagerstown) ; 21(10): 765-771, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32890069

RESUMO

AIMS: The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department. METHODS: All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients. RESULTS: During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged. CONCLUSION: Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.


Assuntos
Anticoagulantes/uso terapêutico , Azitromicina/administração & dosagem , Procedimentos Cirúrgicos Cardíacos , Infecções por Coronavirus , Hidroxicloroquina/administração & dosagem , Pandemias , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral , Complicações Pós-Operatórias , Idoso , Anti-Infecciosos/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Terapia Combinada/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/virologia , Tomografia Computadorizada por Raios X/métodos
10.
BMB Rep ; 53(10): 545-550, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958120

RESUMO

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].


Assuntos
Azitromicina/efeitos adversos , Cardiotoxicidade/etiologia , Cloroquina/efeitos adversos , Células-Tronco Embrionárias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Potenciais de Ação , Animais , Arritmias Cardíacas/induzido quimicamente , Azitromicina/administração & dosagem , Diferenciação Celular , Cloroquina/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Humanos , Camundongos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
11.
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
12.
Cochrane Database Syst Rev ; 8: CD004834, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853410

RESUMO

BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.


Assuntos
Leishmaniose Cutânea/terapia , Administração Oral , Adulto , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Vacina BCG/uso terapêutico , Feminino , Humanos , Hipertermia Induzida , Imunocompetência , Injeções Intramusculares , Injeções Intravenosas , Interferon gama/uso terapêutico , Vacinas contra Leishmaniose/uso terapêutico , Leishmaniose Mucocutânea/terapia , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Int J Antimicrob Agents ; 56(4): 106142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853675

RESUMO

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


Assuntos
Anti-Infecciosos/administração & dosagem , Azitromicina/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Lopinavir/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Ritonavir/administração & dosagem , Idoso , Anti-Infecciosos/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Unidades de Terapia Intensiva , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Lopinavir/efeitos adversos , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Ritonavir/efeitos adversos , Resultado do Tratamento , Troponina I/sangue
15.
Eur J Med Res ; 25(1): 37, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854774

RESUMO

BACKGROUND: COVID-19 is characterized by fast deterioration in the mechanism of cytokine storm. Therefore, treatment with immunomodulating agents should be initiated as soon as hyperinflammation is established. Evidence for the use of tocilizumab (TCZ) in COVID-19 is emerging, but the drug in this setting is used "off label" with limited data on both effectiveness and safety. Therefore, Hospital for Infectious Diseases in Warsaw established a Standard Operating Procedure (SOP) for the use of TCZ in severe COVID-19 cases. CASE PRESENTATION: Here, we present a case of 27-year-old, otherwise healthy man, who was successfully treated with chloroquine, azithromycin, tocilizumab and a standard of care. Initially the magnitude of lung devastation, clinical deterioration and the need for mechanical ventilation suggested unfavorable prognosis. However, we observed complete regression in radiological changes and rapid clinical improvement. Irrespective of this, patient's serum interleukin 6 and aminotransferases remained elevated even after a month from treatment. CONCLUSIONS: An overlapping effect of hyperinflammation, hypoxic organ injury and drug-related toxicity warrants a long-term follow-up for COVID-19 survivors. In addition, residual IL-6 receptors blockage may mask new infections. A standardized approach to follow-up for COVID-19 survivors is urgently needed. Current and future research should also investigate the impact of experimental therapies on lung tissue healing and regeneration, as well as long-term treatment toxicities.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Azitromicina/administração & dosagem , Betacoronavirus , Cloroquina/administração & dosagem , Infecções por Coronavirus/diagnóstico por imagem , Citocinas/metabolismo , Humanos , Inflamação , Masculino , Uso Off-Label , Pandemias , Pneumonia Viral/diagnóstico por imagem , Polônia , Tomografia Computadorizada por Raios X
16.
J Popul Ther Clin Pharmacol ; 27(S Pt 1): e26-e30, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32650356

RESUMO

At the end of December 2019, the Health Commission of the city of Wuhan, China, alerted the World Health Organization (WHO) to a pneumonia cluster in the city. The cause was identified as being a new virus, later named SARS-CoV-2. We can distinguish three clinical phases of the disease with a distinct pathogenesis, manifestations and prognosis. Here, we describe the case of a 45-year-old male, successfully treated for Coronavirus disease (COVID-19). The patient was feeling sick in early April 2020; he had a fever and pharyngodynia. When he came to our COVID hospital, his breathing was normal. The nasopharyngeal swab specimen turned out positive. High-resolution computed tomography (HRCT) showed mild interstitial pneumonia. The patient was admitted to our department and treated with hydroxychloroquine, ritonavir, darunavir, azithromycin and enoxaparin. On day seven of the disease, the patient's respiratory condition got worse as he was developing acute respiratory distress syndrome (ARDS). He was given tocilizumab and corticosteroids and was immediately treated with non-invasive mechanical ventilation (NIMV). His condition improved, and in the ensuing days, the treatment gradually switched to a high-flow nasal cannula (HFNC); after 18 days, the patient's clinical condition was good.The successful results we have been able to obtain are closely associated with avoidance of invasive ventilation that may lead to intensive care unit (ICU)-related superinfections. In our opinion, it is fundamental to understand that COVID-19 is a systemic disease that is a consequence of an overwhelming inflammatory response, which can cause severe medical conditions, even in young patients.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , China , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Darunavir/administração & dosagem , Darunavir/uso terapêutico , Progressão da Doença , Enoxaparina/administração & dosagem , Enoxaparina/uso terapêutico , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico
18.
Cardiol Young ; 30(10): 1482-1485, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32686633

RESUMO

INTRODUCTION AND AIM: Hydroxychloroquine alone or in combination with azithromycin has been increasingly used for patients with coronavirus disease 2019, in both children and adults. Drugs are generally well tolerated in clinical practice; however, both can cause corrected QT prolongation. We aimed to report our experience of QT interval evaluation associated with the use of hydroxychloroquine with concurrent azithromycin among children testing positive for coronavirus disease 2019. METHODS: Our single-centre; retrospective, study evaluated children with coronavirus disease 2019 disease admitted to the Pediatric Department at Sancaktepe Training and Research Hospital Istanbul, Turkey from 10 March, 2020 to 10 April, 2020. The data including demographics, clinical symptoms, co-morbid diseases, laboratory, radiological findings as well as electrocardiographs of the patients were obtained from our records. Electrocardiograms were evaluated before, one day after and at the termination of the treatment. RESULTS: 21 patients aged 9 to 18 years were evaluated. The median age was 170 months (range 112-214), 51.1% of them were girls and 48.9% were boys. Their laboratory results did not reveal any abnormalities. None of them needed intensive care. We did not detect QT prolongation during or at the termination of the treatment. CONCLUSION: We did not detect QT prolongation during or at the termination of the treatment in our patients due to the fact that they were not severely affected by the disease. Patients were treated in our inpatient clinic and none of them required intensive care. Laboratory results were also insignificant. Furthermore, they did not need other medications.


Assuntos
Azitromicina , Infecções por Coronavirus/tratamento farmacológico , Eletrocardiografia/métodos , Hidroxicloroquina , Síndrome do QT Longo , Pneumonia Viral/tratamento farmacológico , Adolescente , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Criança , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/prevenção & controle , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Turquia/epidemiologia
19.
Int J Antimicrob Agents ; 56(1): 106056, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32674929

RESUMO

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


Assuntos
Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Azitromicina/efeitos adversos , Azitromicina/farmacologia , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Projetos de Pesquisa
20.
Trials ; 21(1): 631, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641163

RESUMO

BACKGROUND: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection. METHODS: Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. INTERVENTIONS: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. SECONDARY OUTCOMES: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90. DISCUSSION: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival. TRIAL REGISTRATION: Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).


Assuntos
Azitromicina/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções por Coronavirus/mortalidade , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/mortalidade , Estudos Prospectivos
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