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1.
Ann Rheum Dis ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

2.
Nat Rev Rheumatol ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408338

RESUMO

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

4.
Fetal Diagn Ther ; : 1-8, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296896

RESUMO

OBJECTIVES: To assess the perinatal risks of immune complete congenital heart block (iCCHB) based on the longitudinal analysis of fetal heart rate. METHODS: Retrospective analysis of a cohort of grade III congenital heart block diagnosed in utero, in the absence of associated cardiac defect, with positive maternal serum antibodies. Longitudinal measurements of the fetal heart rate were used to estimate the average slope of ventricular rate as a function of gestational age. We then defined the following prognostic stratification based on longitudinal follow-up observations: the high-rate (HR) group included cases for which all prenatal ventricular rate measurements were above the age-specific mean of our population of iCCHB and the low-rate (LR) group included those with at least one observation below the mean during follow-up. The 2 groups were compared to analyze the potential relationship between prenatal ventricular rate and adverse neonatal outcome defined by in utero or perinatal death, neonatal heart rate <50 bpm, or hemodynamic failure requiring emergency pacing. RESULTS: Forty-four cases were studied. Overall, the average heart rate significantly decreased during gestation from 65 bpm at 20 weeks to 55 bpm at 38 weeks. The HR and LR groups included 18 (41%) and 26 (59%) cases, respectively. Adverse perinatal outcome occurred in 1/18 (6%) and 22/26 (85%) cases in the HR and LR groups, respectively (p < 0.001). In the HR group, 33% of cases remained nonpaced at >6 months. The positive predictive values and negative predictive values for adverse perinatal outcome in the LR group were 85% (22/26) and 94% (17/18), respectively (100 and 80% <30 weeks and 88 and 78% at ≥30 weeks). CONCLUSIONS: The prognostic classification we developed based on longitudinal heart rate assessment may be used in the late 2nd or early 3rd trimester to identify iCCHB cases at high risk of adverse perinatal outcome. This prognostic stratification should help refine counseling and perinatal management earlier in pregnancy instead of waiting for late gestation or predelivery assessment.

5.
Arthritis Rheumatol ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191634

RESUMO

We read with great interest the article by Petri et al. describing the association between hydroxychloroquine (HCQ) blood level and HCQ retinopathy in systemic lupus erythematosus (SLE) (1). Retinopathy occurred in 4.3% of 537 SLE patients. Both mean (p=0.0124) and maximum (p=0.034) HCQ blood levels predicted HCQ retinopathy. By contrast, in a recent case-control study including 23 SLE patients with HCQ retinopathy and 547 controls, no association was found between HCQ blood levels and HCQ retinopathy (2) with a median HCQ blood level of 944ng/mL in the retinopathy group versus 849ng/mL in the control group (p=0.46).

6.
Lupus ; : 961203320973073, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198562

RESUMO

OBJECTIVE: Neonatal lupus syndrome has multisystemic manifestations among which pulmonary involvement has been rarely reported. We describe the clinical presentation, management, and outcome of a series of four neonates who developed reversible pulmonary hypertension associated with auto-immune congenital complete heart block. METHOD: Data from the French registry of neonatal lupus syndrome were retrospectively reviewed. RESULTS: Between 2000 and March 2020, 231 children were included in the French registry, four/73 followed in our institution developed pulmonary hypertension. Diagnosis was suspected on transthoracic echocardiography at a median age of 42 days [range 10-58], and confirmed by right heart catheterization in all; 2 of them where paced at time of diagnosis and 2 were not. All had some degree of hypoxemia and respiratory distress. Hypoxemia was always reversible under O2 et NO. Lung CT demonstrated ground glass anomalies in all. One patient had a lung biopsy consistent with pulmonary hypertension secondary to lung disease. Management included immunosuppressive therapy in 3 associated with sildenafil in 2. Pulmonary hypertension resolved in all at a median age of 4 weeks [range 3-6] after treatment initiation and after one year for the one child who did not receive specific treatment. CONCLUSION: Clinical, hemodynamical, imaging and histological findings advocate for pulmonary hypertension associated with respiratory disease as a rare manifestation of neonatal lupus syndrome.

9.
Ann Rheum Dis ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33055080

RESUMO

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32901293

RESUMO

OBJECTIVE: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE. METHOD: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed. RESULTS: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE. CONCLUSION: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.

11.
Arthritis Res Ther ; 22(1): 223, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977856

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. METHODS: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL. RESULTS: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL). CONCLUSIONS: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

12.
Joint Bone Spine ; : 105075, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32947013

RESUMO

OBJECTIVES: Only scarce data is available regarding pregnancy outcomes in early axSpA, particularly little is known about the impact of disease activity. The objective is to identify (a) the factors associated with the occurrence of a clinical pregnancy during follow-up and (b) the risk factors for an unfavorable pregnancy outcome (e.g. miscarriage, medical termination or pre-term delivery) in an early axSpA population. METHODS: Observational prospective French cohort (DESIR) with 6 years of follow-up including 381 TNFi-naïve women with early axSpA. Factors associated with a clinical pregnancy occurring over follow-up and risk factors for an unfavorable pregnancy outcome were estimated by multivariable multilevel models (i.e. Frailty Shared Models and Mixed Models). RESULTS: During follow-up, 124 pregnancies occurred. Patients who got pregnant during follow-up were more likely to have discontinued their TNFi treatment in the 6 months preceding the pregnancy (HR=2.0 [95% CI 1.1-3.3], P=0.01) and to have an increased CRP at the previous visit (HR=1.7 [95% CI 1.2-2.5], P=0.01). Full-term delivery was by far the most frequent pregnancy outcome (75% of all pregnancies), and only NSAID use in the 6 months prior to the outcome was associated with an unfavorable outcome (OR=2.5 [95% CI 1.1-5.0], P=0.02). No association was found between TNFi use and an unfavorable pregnancy outcome. CONCLUSION: Full-term delivery was the most frequent pregnancy outcome. NSAID use within 6 months of outcome, but not TNFi use, was associated with an unfavorable pregnancy outcome in this early axSpA cohort.

13.
Circ Arrhythm Electrophysiol ; 13(10): e008686, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907357

RESUMO

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.


Assuntos
Antivirais/administração & dosagem , Eletrocardiografia , Coração Fetal/efeitos dos fármacos , Bloqueio Cardíaco/congênito , Frequência Cardíaca/efeitos dos fármacos , Hidroxicloroquina/administração & dosagem , Antivirais/efeitos adversos , Antivirais/sangue , Cardiotoxicidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Sangue Fetal/metabolismo , Coração Fetal/fisiopatologia , Idade Gestacional , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Bloqueio Cardíaco/prevenção & controle , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/sangue , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
16.
Orphanet J Rare Dis ; 15(1): 180, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641076

RESUMO

BACKGROUND: Congenital hemolytic anemia constitutes a heterogeneous group of rare genetic disorders of red blood cells. Diagnosis is based on clinical data, family history and phenotypic testing, genetic analyses being usually performed as a late step. In this study, we explored 40 patients with congenital hemolytic anemia by whole exome sequencing: 20 patients with hereditary spherocytosis and 20 patients with unexplained hemolysis. RESULTS: A probable genetic cause of disease was identified in 82.5% of the patients (33/40): 100% of those with suspected hereditary spherocytosis (20/20) and 65% of those with unexplained hemolysis (13/20). We found that several patients carried genetic variations in more than one gene (3/20 in the hereditary spherocytosis group, 6/13 fully elucidated patients in the unexplained hemolysis group), giving a more accurate picture of the genetic complexity of congenital hemolytic anemia. In addition, whole exome sequencing allowed us to identify genetic variants in non-congenital hemolytic anemia genes that explained part of the phenotype in 3 patients. CONCLUSION: The rapid development of next generation sequencing has rendered the genetic study of these diseases much easier and cheaper. Whole exome sequencing in congenital hemolytic anemia could provide a more precise and quicker diagnosis, improve patients' healthcare and probably has to be democratized notably for complex cases.

17.
J Am Coll Cardiol ; 76(3): 292-302, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32674792

RESUMO

BACKGROUND: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB). OBJECTIVES: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. METHODS: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. RESULTS: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). CONCLUSIONS: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573).

19.
Clin Exp Rheumatol ; 38(4): 783-791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32573408

RESUMO

OBJECTIVES: Fluorinated steroids are largely the therapeutic approach of autoimmune mediated congenital heart block (CHB). We performed a meta-analysis to assess the efficacy of fluorinated steroids for the treatment of CHB. METHODS: Studies evaluating the efficacy of fluorinated steroids versus no treatment in CHB patients were identified in electronic databases. Random-effects model was used to pool odds ratio (OR) (with 95% CI) of live births as the primary outcome. ORs of CHB progression, pacemaker implantation and extranodal disease were the secondary outcome. Subgroup analysis according to CHB grade and study type was performed. RESULTS: Data from nine studies involving 747 patients were analysed. The overall live birth rates were 86.8% and 86.7%, respectively, in the fluorinated steroids exposed foetuses and in the non-exposed ones. Fluorinated steroids did not ameliorate overall survival in CHB (OR 1.02; 95% CI: 0.65-1.61) with any significant statistical heterogeneity between studies (I2 0%, p=0.45). No significant differences for the progression of CHB, the pacing and the presence of extranodal disease were observed. Subgroup analysis revealed a significant protective role of fluorinated steroids for survival in 3rd degree CHB and for pacing in monocentric studies, OR 4.07; 95% CI: 1.10-15.08 and OR 0.15; 95% CI: 0.02-0.99, respectively. CONCLUSIONS: This meta-analysis shows that fluorinated steroids are not superior to any treatment in patients with CHB in terms of live birth, prevention of progression of incomplete CHB, pacemaker implantation and extranodal disease. Thus, considering their side effects, their use in CHB patients should be discouraged.


Assuntos
Bloqueio Cardíaco , Esteroides Fluorados , Glucocorticoides , Bloqueio Cardíaco/congênito , Humanos
20.
BMJ ; 369: m1844, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409486

RESUMO

OBJECTIVE: To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen. DESIGN: Comparative observational study using data collected from routine care. SETTING: Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020. PARTICIPANTS: 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care. INTERVENTIONS: Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group). MAIN OUTCOME MEASURES: The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting. RESULTS: In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. CONCLUSIONS: Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Adulto Jovem
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