Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial.

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]). Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. Funding: COALITION COVID-19 Brazil and EMS.

Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

Predictive Factors of Gastroesophageal Reflux Disease in Bariatric Surgery: a Controlled Trial Comparing Sleeve Gastrectomy with Gastric Bypass.

OBJECTIVE: To evaluate the impact of laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) on gastroesophageal reflux disease (GERD) in patients with obesity. METHODS: Patients with class II or III obesity were treated with LSG or LRYGB. Procedure choice was based on patients and surgeon preferences. GERD symptoms, endoscopy, barium swallow X-ray, esophageal manometry, and 24-h pH monitoring were obtained before and 1 year after surgery. RESULTS: Seventy-five patients underwent surgery (83% female, 39.3 ± 12.1 years, BMI of 41.5 ± 5.1 kg/m2): 35 (46.7%) had LSG and 40 (53.3%) LRYGB. LSG patients had lower BMI (40.3 ± 4.0 kg/m2 vs. 42.7 ± 5.7 kg/m2; p = 0.041) and trend toward lower prevalence of GERD (20% vs. 40%; p = 0.061). One year after surgeries, GERD was more frequent in LSG patients (74% vs. 25%; p < 0.001) and all LSG patients with preoperative GERD continue to have GERD postoperatively. De novo GERD occurred in 19 of 28 (67.9%) of LSG patients and 4 of 24 (16.7%) patients treated with LRYGB (OR 10.6, 95%CI 2.78-40.1). Independent predictors for post-operative GERD were as follows: LSG (OR 12.3, 95%CI 2.9-52.5), preoperative esophagitis (OR 8.5, 95% CI 1.6-44.8), and age (OR 2.0, 95%CI 1.1-3.4). CONCLUSIONS: One year after surgery, persistent or de novo GERD were substantially more frequent in patients treated with LSG compared with LRYGB. LSG was the strongest predictor for GERD in our trial. Preoperative counseling and choice of bariatric surgical options must include a detailed assessment and discussion of GERD-related surgical outcomes.

Percutaneous balloon aortic valvuloplasty in a pregnant adolescent.

We report the case of a 16-year-old pregnant patient with severe aortic stenosis and pulmonary congestion clinically uncontrolled, in whom percutaneous balloon aortic valvuloplasty was used as the first choice of treatment in an emergency procedure. The clinical findings, pathophysiology, diagnostic features, and indications for percutaneous treatment are reported. Severe congenital aortic stenosis is rare in children and young individuals. Bicuspid aortic valve occurs in 3% to 6% of patients with congenital heart disease; when associated with commissural fusion, significant stenosis may be present in childhood. The association of severe congenital aortic stenosis and pregnancy is difficult to control clinically, carrying a high risk of maternal and fetal mortality, mainly when manifested with symptoms of pulmonary congestion 1,2.

Percutaneous balloon aortic valvuloplasty in a pregnant adolescent / Valvoplastia aórtica percutânea em adolescente gestante

Relatamos um caso em que a valvoplastia aórtica percutânea foi utilizada como primeira escolha, em procedimento de urgência, para o tratamento de estenose aórtica grave em paciente gestante de 16 anos, com congestão pulmonar sem controle clínico. Descrevem-se o quadro clínico, a fisiopatologia, os aspectos diagnósticos e indicações do tratamento percutâneo. A estenose valvar aórtica congênita, quando grave, é rara em crianças e jovens. A valva aórtica bicúspide ocorre em 3 por cento a 6 por cento com doença cardíaca congênita e, quando relacionada com fusão comissural, pode haver estenose importante já na infância. A associação de estenose aórtica congênita grave com gestação é de difícil controle clínico e alto risco de mortalidade materna e fetal, principalmente quando se manifesta com sintomas de congestão pulmonar.