An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial.

BACKGROUND: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization. RESULTS: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days. CONCLUSIONS: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

Primary results of the brazilian registry of atherothrombotic disease (NEAT).

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease.ClinicalTrials.gov NCT04677725.

Antivirals for adult patients hospitalised with SARS-CoV-2 infection: a randomised, phase II/III, multicentre, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn trial.

Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients. Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087. Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups. Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less. Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).

Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. OBJECTIVES: To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. DATA SOURCES: PubMed, Embase, Cochrane Library, and MedRxiv. STUDY ELIGIBILITY CRITERIA: Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). METHODS: Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. PARTICIPANTS: Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. RESULTS: All but two studies included data with only indirect evidence for the comparison of interest. CONCLUSIONS: Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.

Evaluation of the diagnostic management of deep vein thrombosis in the emergency department of a tertiary hospital in Santa Catarina, Brazil: a cross-sectional study.

Background: Venous thromboembolism is an entity that encompasses both deep vein thrombosis and pulmonary thromboembolism. Although protocols for the diagnosis of these diseases are well defined, there is evidence of inappropriate use of diagnostic resources. Objectives: To define the epidemiological profiles of patients admitted to the emergency department with suspected deep vein thrombosis, to determine rates of inappropriate ordering of D-dimer assays and color venous Doppler echocardiography of the lower limbs, and to identify whether these requests followed the recommendations contained in the 2015 Brazilian Society of Angiology and Vascular Surgery guidelines. Methods: We conducted a cross-sectional observational study that retrospectively evaluated 168 patients with suspected deep vein thrombosis for whom D-dimer assays were requested. The most common risk factors were measured and the pretest probability was calculated with the Wells score. The epidemiological profile of these patients and the rates of inappropriate D-dimer testing were assessed using descriptive statistics. Results: The D-dimer requests were inadequate in 55 (32.7%) patients. Venous color Doppler ultrasound was used to examine the lower limbs of 14 (8.3%) of the patients with a low probability according to the Wells score and a negative D-dimer result. No additional diagnostic methods were used in 19 (11.3%) of those with a low probability according to the Wells score and a high D-dimer result. There was unnecessary use of CDUS in 35 (20.8%) cases. The overall rate of inappropriate workup was 53.5%. Conclusions: Differences were found between clinical practice and the recommendations for diagnostic evaluation of patients with suspected deep vein thrombosis, with inappropriate use of diagnostic tests.

Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: A Bayesian Reanalysis of a Previous Meta-analysis.

Importance: A World Health Organization (WHO) meta-analysis found that tocilizumab was associated with reduced mortality in hospitalized patients with COVID-19. However, uncertainty remains concerning the magnitude of tocilizumab's benefits and whether its association with mortality benefit is similar across respiratory subgroups. Objective: To use bayesian methods to assess the magnitude of mortality benefit associated with tocilizumab and the differences between respiratory support subgroups in hospitalized patients with COVID-19. Design, Setting, and Participants: A bayesian hierarchical reanalysis of the WHO meta-analysis of tocilizumab studies published in 2020 and 2021 was performed. Main results were estimated using weakly informative priors to exert little influence on the observed data. The robustness of these results was evaluated using vague and informative priors. The studies featured in the meta-analysis were randomized clinical tocilizumab trials of hospitalized patients with COVID-19. Only patients receiving corticosteroids were included. Interventions: Usual care plus tocilizumab in comparison with usual care or placebo. Main Outcomes and Measures: All-cause mortality at 28 days after randomization. Results: Among the 5339 patients included in this analysis, most were men, with mean ages between 56 and 66 years. There were 2117 patients receiving simple oxygen only, 2505 receiving noninvasive ventilation (NIV), and 717 receiving invasive mechanical ventilation (IMV) in 15 studies from multiple countries and continents. Assuming weakly informative priors, the overall odds ratios (ORs) for survival were 0.70 (95% credible interval [CrI], 0.50-0.91) for patients receiving simple oxygen only, 0.81 (95% CrI, 0.63-1.03) for patients receiving NIV, and 0.89 (95% CrI, 0.61-1.22) for patients receiving IMV, respectively. The posterior probabilities of any benefit (OR <1) were notably different between patients receiving simple oxygen only (98.9%), NIV (95.5%), and IMV (75.4%). The posterior probabilities of a clinically meaningful association (absolute mortality risk difference >1%) were greater than 95% in patients receiving simple oxygen only and greater than 90% in patients receiving NIV. In contrast, the posterior probability of this clinically meaningful association was only approximately 67% in patients receiving IMV. The probabilities of tocilizumab superiority in the simple oxygen only subgroup compared with the NIV and IMV subgroups were 85% and 90%, respectively. Predictive intervals highlighted that only 72.1% of future tocilizumab IMV studies would show benefit. The conclusions did not change with different prior distributions. Conclusions and Relevance: In this bayesian reanalysis of a previous meta-analysis of 15 studies of hospitalized patients with COVID-19 treated with tocilizumab and corticosteroids, use of simple oxygen only and NIV was associated with a probability of a clinically meaningful mortality benefit from tocilizumab. Future research should clarify whether patients receiving IMV also benefit from tocilizumab.

Avaliação do manejo diagnóstico de trombose venosa profunda no departamento de emergência de um hospital terciário em Santa Catarina: um estudo transversal / Evaluation of the diagnostic management of deep vein thrombosis in the emergency department of a tertiary hospital in Santa Catarina, Brazil: a cross-sectional study

Resumo Contexto O tromboembolismo venoso é uma entidade que compreende a trombose venosa profunda e o tromboembolismo pulmonar. Embora os protocolos para diagnóstico dessas doenças estejam bem definidos, evidências têm demonstrado uso inadequado de recursos diagnósticos. Objetivos Definir o perfil epidemiológico dos pacientes com suspeita de trombose venosa profunda admitidos na emergência, determinar taxas de inadequação nas solicitações de D-dímero e eco-Doppler colorido venoso de membros inferiores e identificar se essas solicitações seguiram as recomendações da diretriz da Sociedade Brasileira de Angiologia e Cirurgia Vascular de 2015. Métodos Estudo observacional transversal que avaliou retrospectivamente 168 pacientes com suspeita de trombose venosa profunda, aos quais foi solicitado D-dímero. Foram mensurados os fatores de risco mais comuns e a probabilidade pré-teste pelo escore de Wells. O perfil epidemiológico desses pacientes, assim como as taxas de inadequação, foram avaliados por meio de uso de estatística descritiva. Resultados Em 55 (32,7%) casos, as solicitações de D-dímero foram inadequadas. Em 14 (8,3%) pacientes com baixa probabilidade no escore de Wells e D-dímero negativo, houve uso desnecessário de eco-Doppler colorido venoso de membros inferiores, sendo que, em 19 (11,3%) daqueles com baixa probabilidade no escore de Wells e D-dímero elevado, não houve complementação diagnóstica. O uso de eco-Doppler colorido venoso foi inadequado em 35 (20,8%) casos. A taxa global de inadequação foi de 53,5%. Conclusões Constataram-se divergências entre a prática clínica e as recomendações propostas para avaliação diagnóstica nos pacientes com suspeita de trombose venosa profunda devido ao uso inadequado de testes diagnósticos.

Abstract Background Venous thromboembolism is an entity that encompasses both deep vein thrombosis and pulmonary thromboembolism. Although protocols for the diagnosis of these diseases are well defined, there is evidence of inappropriate use of diagnostic resources. Objectives To define the epidemiological profiles of patients admitted to the emergency department with suspected deep vein thrombosis, to determine rates of inappropriate ordering of D-dimer assays and color venous Doppler echocardiography of the lower limbs, and to identify whether these requests followed the recommendations contained in the 2015 Brazilian Society of Angiology and Vascular Surgery guidelines. Methods We conducted a cross-sectional observational study that retrospectively evaluated 168 patients with suspected deep vein thrombosis for whom D-dimer assays were requested. The most common risk factors were measured and the pretest probability was calculated with the Wells score. The epidemiological profile of these patients and the rates of inappropriate D-dimer testing were assessed using descriptive statistics. Results The D-dimer requests were inadequate in 55 (32.7%) patients. Venous color Doppler ultrasound was used to examine the lower limbs of 14 (8.3%) of the patients with a low probability according to the Wells score and a negative D-dimer result. No additional diagnostic methods were used in 19 (11.3%) of those with a low probability according to the Wells score and a high D-dimer result. There was unnecessary use of CDUS in 35 (20.8%) cases. The overall rate of inappropriate workup was 53.5%. Conclusions Differences were found between clinical practice and the recommendations for diagnostic evaluation of patients with suspected deep vein thrombosis, with inappropriate use of diagnostic tests.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.

Impacto do covid nas cirurgias de trocas valvares no Brasil / Impact of covid on valve replacement surgeries in Brazil

INTRODUÇÃO: Com o surgimento do novo coronavírus (COVID-19) em dezembro de 2019, diversas áreas da medicina sofreram com o impacto da pandemia. Na cardiologia, a redução da procura por atendimento gerou consequências imediatas no número de procedimentos e cirurgias, com consequente aumento da letalidade das doenças cardiovasculares, inclusive no Brasil. Ao longo do último ano, o impacto do COVID-19 na mortalidade dos pacientes submetidos a cirurgias cardíacas tornou- -se OBJETO DE ESTUDO. Em março de 2021, uma análise prospectiva e multicêntrica identificou aumento da mortalidade neste grupo de pacientes. O objetivo do atual estudo é avaliar eventos adversos em pacientes que foram submetidos à cirurgia de troca valvar em serviço terciário brasileiro, com diagnóstico de COVID-19 na internação, antes ou após o procedimento. MÉTODOS: Coorte retrospectiva de pacientes internados pelo pronto-socorro submetidos à cirurgia de troca valvar de urgência, de maneira consecutiva, durante a pandemia (01 de abril de 2020 à 31 de março de 2021). Eventos intra-hospitalares foram comparados entre pacientes não contaminados pelo COVID-19 com os que testaram positivo (RT-PCR), pré ou pós procedimento cirúrgico. Variáveis categóricas foram apresentadas em frequências e porcentagens, enquanto as variáveis numéricas foram descritas em medidas de tendência central. Foi realizada análise estatística bivariada e considerou-se estatisticamente significativo o valor de p < 0,05 bicaudal. RESULTADOS: De Abril de 2020 à Março de 2021, foram realizadas 278 cirurgias de trocavalvar no instituto. Destes pacientes cerca de 60% deles foram contaminados antes do procedimento. Cerca de 53% na tabela 1 observa-se o perfil epidemiológico dos pacientes e as características de base, seguindo pelos desfechos na tabela 2. Foi observado maior tendência à mortalidade intra-hospitalar, aumento da necessidade de hemodiálise e período mais prolongado de internação hospitalar (31,1 vs 15,3 dias entre cirurgia e alta, p < 0,001), nos pacientes infectados pelo COVID-19. CONCLUSÃO: O atual estudo é o primeiro a avaliar exclusivamente o impacto da infecção pelo novo coronavírus nas cirurgias de troca valvar no Brasil. Os dados sugerem que a presença da doença pode estar associada a aumento da mortalidade, necessidade de hemodiálise e aumento considerável no tempo de internação. Mais estudos são necessários, com maior número amostral, para avaliar com mais precisão o verdadeiro impacto do COVID-19 nas cirurgias de troca valvar.

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

Factors associated with mortality among elderly people hospitalized due to femoral fractures.

OBJECTIVE: To analyze factors associated with mortality among elderly people hospitalized in a single-center regional hospital due to femoral fractures. METHODS: This was a retrospective cohort study. Patients aged 60 years or over who were hospitalized with a diagnosis of femoral fracture (ICD S72) between 2008 and 2013 were selected through the electronic medical records. RESULTS: The study evaluated 195 individuals of mean age 78.5 ± 9.6 years; females predominated (68.2%). The main mechanism for falls was low-energy (87.2%). Surgery was performed on 93.3% of the patients; the mean length of hospital stay was 13.6 ± 7.5 days and the mean waiting time for the surgery was 7.7 ± 4.2 days. The prevalence of mortality was 14.4%, and this occurred mostly among older individuals (p = 0.029); patients with leukocytosis (p < 0.001); those who needed intensive care (p < 0.001); and those who did not undergo surgery (p < 0.001). The mean survival was significantly longer among patients who underwent surgery and shorter among those who needed intensive care. CONCLUSION: Women predominated among the hospitalizations, and the degree of leukocytosis associated with advanced age presented a relationship with mortality, independent of the type of lesion or surgical procedure. More studies still need to be conducted in order to assess other factors associated with mortality.

OBJETIVO: Analisar os fatores associados à mortalidade em idosos hospitalizados por fratura de fêmur em um hospital unicêntrico regional. MÉTODOS: Estudo de coorte retrospectiva. Foram selecionados, por meio do prontuário eletrônico, pacientes internados com diagnóstico de fratura de fêmur (CID S72) com 60 anos ou mais de 2008 a 2013. RESULTADOS: Foram avaliados 195 indivíduos com idade média de 78,5 ± 9,6 e o gênero feminino foi mais prevalente (68,2%). O principal mecanismo de queda foi o de baixa energia (87,2%), a feitura de cirurgia foi de 93,3%, o tempo de internação médio foi de 13,6 ± 7,5 dias, o tempo de espera para a cirurgia médio foi de 7,7 ± 4,2 dias. A prevalência de mortalidade foi de 14,4%, ocorreu principalmente nos indivíduos mais idosos (p = 0,029), com leucocitose (p < 0,001), com necessidade de cuidados intensivos (p < 0,001) e que não foram submetidos a cirurgia (p < 0,001). A sobrevida média foi significativamente maior nos pacientes submetidos a cirurgia e inversamente nos pacientes que necessitaram da unidade de terapia intensiva. CONCLUSÃO: As mulheres predominaram nas internações e o grau de leucocitose associado a idade avançada apresentou relação com a mortalidade, independentemente do tipo de lesão e procedimento cirúrgico. Ainda devem ser feitos mais estudos para avaliar outros fatores associados à mortalidade.

Factors associated with mortality among elderly people hospitalized due to femoral fractures / Fatores associados à mortalidade em idosos hospitalizados por fraturas de fêmur

ABSTRACT OBJECTIVE: To analyze factors associated with mortality among elderly people hospitalized in a single-center regional hospital due to femoral fractures. METHODS: This was a retrospective cohort study. Patients aged 60 years or over who were hospitalized with a diagnosis of femoral fracture (ICD S72) between 2008 and 2013 were selected through the electronic medical records. RESULTS: The study evaluated 195 individuals of mean age 78.5 ± 9.6 years; females predominated (68.2%). The main mechanism for falls was low-energy (87.2%). Surgery was performed on 93.3% of the patients; the mean length of hospital stay was 13.6 ± 7.5 days and the mean waiting time for the surgery was 7.7 ± 4.2 days. The prevalence of mortality was 14.4%, and this occurred mostly among older individuals (p = 0.029); patients with leukocytosis (p < 0.001); those who needed intensive care (p < 0.001); and those who did not undergo surgery (p < 0.001). The mean survival was significantly longer among patients who underwent surgery and shorter among those who needed intensive care. CONCLUSION: Women predominated among the hospitalizations, and the degree of leukocytosis associated with advanced age presented a relationship with mortality, independent of the type of lesion or surgical procedure. More studies still need to be conducted in order to assess other factors associated with mortality.

RESUMO OBJETIVO: Analisar os fatores associados à mortalidade em idosos hospitalizados por fratura de fêmur em um hospital unicêntrico regional. MÉTODOS: Estudo de coorte retrospectiva. Foram selecionados, por meio do prontuário eletrônico, pacientes internados com diagnóstico de fratura de fêmur (CID S72) com 60 anos ou mais de 2008 a 2013. RESULTADOS: Foram avaliados 195 indivíduos com idade média de 78,5 ± 9,6 e o gênero feminino foi mais prevalente (68,2%). O principal mecanismo de queda foi o de baixa energia (87,2%), a feitura de cirurgia foi de 93,3%, o tempo de internação médio foi de 13,6 ± 7,5 dias, o tempo de espera para a cirurgia médio foi de 7,7 ± 4,2 dias. A prevalência de mortalidade foi de 14,4%, ocorreu principalmente nos indivíduos mais idosos (p = 0,029), com leucocitose (p < 0,001), com necessidade de cuidados intensivos (p < 0,001) e que não foram submetidos a cirurgia (p < 0,001). A sobrevida média foi significativamente maior nos pacientes submetidos a cirurgia e inversamente nos pacientes que necessitaram da unidade de terapia intensiva. CONCLUSÃO: As mulheres predominaram nas internações e o grau de leucocitose associado a idade avançada apresentou relação com a mortalidade, independentemente do tipo de lesão e procedimento cirúrgico. Ainda devem ser feitos mais estudos para avaliar outros fatores associados à mortalidade.

Rotator cuff injuries and factors associated with reoperation.

OBJECTIVE: To evaluate the prevalence of rotator cuff tears and describe the profile of reoperated patients, causes of repeated tendon tears, tear evolution and range of times between surgical procedures. METHOD: This was a cross-sectional study involving 604 surgical procedures performed at two regional referral hospitals between January 2006 and December 2012. After approval by the ethics committee, data describing the patients' epidemiological profile were gathered at a single time, using Cofield's classification to measure the extent of the tears, all of which underwent arthroscopic surgery. The data were entered into Epi Info 3.5.3 and were analyzed using SPSS version 18.0. RESULTS: Among the 604 surgical procedures, females were affected in more cases (351; 58.1%). When the dominant limb was the right limb, it was affected in 90% of the cases (p < 0.05). The supraspinatus tendon was affected in 574 cases (95%) and the tears were of medium size in 300 cases (49.7%). Eighteen reoperations were performed (2.98%) and the upper right limb was the most affected (66.6%). The cause was non-traumatic in 12 patients. The repeated tears were mostly smaller (44%), and the length of time between the two surgical procedures ranged from 6 to 298 weeks. CONCLUSION: Female gender, smaller extent in the second procedure and non-traumatic cause were found in most of the cases analyzed.

OBJETIVO: Avaliar a prevalência de LMR, descrever o perfil do paciente reoperado, a causa da rerruptura tendínea, a evolução da lesão e a variação de tempo entre os procedimentos cirúrgicos. MÉTODOS: Estudo com delineamento transversal, que envolveu 604 eventos cirúrgicos feitos entre janeiro de 2006 e dezembro de 2012, em dois hospitais de referência regional. Após aprovação pelo comitê de ética, os dados foram coletados em um único momento, descreveu-se o perfil epidemiológico dos pacientes e usou-se a classificação de Cofield para mensurar a extensão das lesões, as quais foram operadas por via artroscópica em todos os pacientes. Os dados foram digitados no programa Epinfo versão 3.5.3®, e analisados no SPSS versão 18.0®. RESULTADOS: Entre os 604 procedimentos, o sexo feminino esteve predominantemente acometido com 351 (58,1%) e quando o membro dominante foi o direito ele esteve acometido em 90% dos casos (p < 0,05). O tendão supraespinhal foi acometido em 574 (95%) casos e as lesões foram de tamanho médio em 300 (49,7%) casos. Foram 18 (2,98%) reoperações e o membro superior direito foi o mais acometido (66,6%), com causa não traumática em 12 pacientes. As relesões foram em sua maioria menores (44%), com o tempo entre os dois procedimentos cirúrgicos que variou entre seis e 298 semanas. CONCLUSÃO: Sexo feminino, extensão menor no segundo procedimento e causa não traumática foram encontrados na maior parte dos casos analisados.

Rotator cuff injuries and factors associated with reoperation / Lesões do manguito rotador e fatores associados à reoperação

OBJECTIVE: To evaluate the prevalence of rotator cuff tears and describe the profile of reoperated patients, causes of repeated tendon tears, tear evolution and range of times between surgical procedures. METHOD: This was a cross-sectional study involving 604 surgical procedures performed at two regional referral hospitals between January 2006 and December 2012. After approval by the ethics committee, data describing the patients' epidemiological profile were gathered at a single time, using Cofield's classification to measure the extent of the tears, all of which underwent arthroscopic surgery. The data were entered into Epi Info 3.5.3 and were analyzed using SPSS version 18.0. RESULTS: Among the 604 surgical procedures, females were affected in more cases (351; 58.1%). When the dominant limb was the right limb, it was affected in 90% of the cases (p < 0.05). The supraspinatus tendon was affected in 574 cases (95%) and the tears were of medium size in 300 cases (49.7%). Eighteen reoperations were performed (2.98%) and the upper right limb was the most affected (66.6%). The cause was non-traumatic in 12 patients. The repeated tears were mostly smaller (44%), and the length of time between the two surgical procedures ranged from 6 to 298 weeks. CONCLUSION: Female gender, smaller extent in the second procedure and non-traumatic cause were found in most of the cases analyzed.

OBJETIVO: Avaliar a prevalência de LMR, descrever o perfil do paciente reoperado, a causa da rerruptura tendínea, a evolução da lesão e a variação de tempo entre os procedimentos cirúrgicos. MÉTODOS: Estudo com delineamento transversal, que envolveu 604 eventos cirúrgicos feitos entre janeiro de 2006 e dezembro de 2012, em dois hospitais de referência regional. Após aprovação pelo comitê de ética, os dados foram coletados em um único momento, descreveu-se o perfil epidemiológico dos pacientes e usou-se a classificação de Cofield para mensurar a extensão das lesões, as quais foram operadas por via artroscópica em todos os pacientes. Os dados foram digitados no programa Epinfo versão 3.5.3(r), e analisados no SPSS versão 18.0(r). RESULTADOS: Entre os 604 procedimentos, o sexo feminino esteve predominantemente acometido com 351 (58,1%) e quando o membro dominante foi o direito ele esteve acometido em 90% dos casos (p < 0,05). O tendão supraespinhal foi acometido em 574 (95%) casos e as lesões foram de tamanho médio em 300 (49,7%) casos. Foram 18 (2,98%) reoperações e o membro superior direito foi o mais acometido (66,6%), com causa não traumática em 12 pacientes. As relesões foram em sua maioria menores (44%), com o tempo entre os dois procedimentos cirúrgicos que variou entre seis e 298 semanas. CONCLUSÃO: Sexo feminino, extensão menor no segundo procedimento e causa não traumática foram encontrados na maior parte dos casos analisados.

Depressive Symptoms and Associated Factors among People Living with HIV/AIDS.

The purpose of this study was to evaluate the prevalence of depressive symptoms and associated variables among people living with HIV/AIDS (PLWHA) in a specialized treatment center in a city located in southern Brazil. A cross-sectional study was conducted using the Beck Depression Inventory to assess the presence of depressive symptoms. The prevalence of depressive symptoms was 53.5% among the surveyed population, which supports the idea that depressive symptoms are more common among PLWHA, mainly if compared with the general population. It was observed that 57.7% of the study participants were with depressive symptoms and did not take any psychiatric medication and 100% did not undergo psychotherapy, which indicates undertreatment. There was no statistically significant difference in the mean CD4 count between patients with depressive symptoms (484.1  ±  353) and patients without depressive symptoms (528.4  ±  263). Further actions should be taken to improve the care for PLWHA. The interface between psychology, psychiatry, and internal medicine is of utmost importance to provide a more humanized care, in which the psychosocial, psychological, and psychiatric aspects are not neglected.