Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients: a retrospective study with inverse probability of treatment weighting analysis.

BACKGROUND: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality. METHODS: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use. RESULTS: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24-1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21-1.78). CONCLUSIONS: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

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.

Phase Angle Evaluation of Lung Disease Patients and Its Relationship with Nutritional and Functional Parameters.

BACKGROUND: This study aimed to determine the value of phase angle (PhA) in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) and its association with nutritional and functional parameters. METHODS: A cross-sectional study of 77 patients under follow-up at the pulmonary outpatient clinic of a public hospital. Anthropometric measurements and functional assessments of physical and pulmonary capacity were performed, and a regular physical activity questionnaire was administered. RESULTS: The sample consisted of 38 patients with COPD (mean age, 63.8 ± 9.9 years; 68.4% female) and 39 patients with PH (mean age, 46.6 ± 14.4 years; 79.5% female). There was no difference in anthropometric measurements between patients with COPD and PH. Patients with COPD had mild to moderate limitations of pulmonary function, while patients with PH had only mild limitations (p < 0.01). Although the median distance covered in the 6-minute walk test (6MWT) was different between the COPD and PH groups (p < 0.05), it was considered adequate for these populations. Mean PhA was within the range considered adequate in patients with COPD (6.3°±1°) and PH (6.2°±0.8°) (p > 0.05). In the statistical analyses, although the correlations were weak, adequate PhA correlated with fat free mass index, 6MWT, disease staging, forced vital capacity, and forced expiratory volume in the first second. CONCLUSION: The anthropometric profile of both patient groups was very similar, and PhA values were within the expected range. Despite weak correlations, PhA is a clinical component to be followed and investigated in patients with lung disease.

Risk assessment validation in patients with pulmonary arterial hypertension: Data from a Southern Brazil registry (RESPHIRAR study).

Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Registries are a valuable tool in the research of rare conditions such as PAH. Moreover, the risk assessment strategy has been validated in European and North American registries and has been reported to provide an accurate prediction of mortality and the clinical advantage of reaching low-risk status. However, there is no available data from Brazil. Thus, the aim of the present study was to describe the characteristics of a sample of PAH from Southern Brazil and to retrospectively validate the risk assessment at our population. The RESPHIRAR is a retrospective and multicentric registry on pulmonary hypertension. With a join collaboration from nine centers in Southern Brazil, demographics, clinical presentation, and hemodynamics data of PAH were collected between 2007 and 2017. Moreover, the REVEAL 2.0 and REVEAL 2.0 Lite risk assessments were validated in our population. Overall, 370 PAH patients were included in the present study. Patients were predominantly female (78.5%) and had a mean age of 41.8 ± 18.8 years. Most patients (33.4%) had idiopathic PAH, 30.2% had PAH associated with congenital heart disease, and 23.5% had PAH associated with connective tissue disease. The low-risk group showed significantly lower mortality than the intermediated- or high-risk group at diagnosis (p < 0.05). In conclusion, our data suggest that REVEAL 2.0 and REVEAL 2.0 Lite risk assessments can predict mortality risk in PAH patients in Southern Brazil.

Impact of impaired pulmonary function on clinical outcomes in survivors of severe COVID-19 without pre-existing respiratory disease.

OBJECTIVE: To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease. METHODS: This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities. RESULTS: At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect. CONCLUSIONS: The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

D-dimer levels in stable COPD patients: a case-control study.

BACKGROUND: High D-dimer levels have been detected in patients with chronic obstructive pulmonary disease (COPD) exacerbation, irrespective of presence of venous thromboembolism. On the other hand, there is a continuing debate about the diagnostic efficiency of D-dimer tests in patients with stable COPD. OBJECTIVES: We aimed to investigate if basic laboratory investigations suggest hypercoagulability state in stable COPD patients, and if there is an association with D-dimer levels and pulmonary function tests. METHODS: We conducted a case-control study. COPD patients and controls were matched for sex and age in a 2:1 matching ratio. D-dimer levels and pulmonary function tests were performed in COPD patients and controls. RESULTS: A total of 58 COPD patients and 30 controls met the inclusion criteria and were included in the analysis. The median of D-dimers was 0.24 ng/mL (IQR: 0.21-0.36 ng/mL) in COPD group and 0.17 ng/mL (IQR: 0.12-0.24 ng/mL) in control group. This difference was not statistically significant (p = 0.102). Using bivariate correlations, we found significant positive correlations between BMI and D-dimers in COPD patients (r = 0.3, p = 0.024). CONCLUSIONS: We found that levels of D-dimers in stable COPD were not different as compared to control subjects. Our results also suggest that BMI could lead to disturbances in coagulation system.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

Severe hepatopulmonary syndrome with hypoxemia refractory to liver transplant: Recovery after 67 days of ECMO support.

Hepatopulmonary syndrome (HPS) is a complication of end stage liver disease (ESLD) and is manifested by severe hypoxemia, which usually responds to liver transplantation (LT). As compared to patients undergoing LT for other etiologies, patients with HPS present an increased risk of postoperative morbidity and mortality. There is no effective treatment for patients whose hypoxemia does not respond to LT. This subset of patients is at a highly increased risk of death. There are very few reports on the use of extracorporeal membrane oxygenation (ECMO) in this setting with rapid response. However, there is no prior report of ECMO utilization for longer than 4 weeks. We present the case of a 17 year-old male patient who underwent LT for ESLD secondary to chronic portal vein thrombosis and HPS. He received a liver from a deceased donor and presented with severe HPS after LT, requiring ECMO support for 67 days. The patient was discharged home and is breathing in ambient air. He is currently asymptomatic and has a normal liver function.

Pulmonology approach in the investigation of chronic unexplained dyspnea.

Chronic unexplained dyspnea and exercise intolerance represent common, distressing symptoms in outpatients. Clinical history taking and physical examination are the mainstays for diagnostic evaluation. However, the cause of dyspnea may remain elusive even after comprehensive diagnostic evaluation-basic laboratory analyses; chest imaging; pulmonary function testing; and cardiac testing. At that point (and frequently before), patients are usually referred to a pulmonologist, who is expected to be the main physician to solve this conundrum. In this context, cardiopulmonary exercise testing (CPET), to assess physiological and sensory responses from rest to peak exercise, provides a unique opportunity to unmask the mechanisms of the underlying dyspnea and their interactions with a broad spectrum of disorders. However, CPET is underused in clinical practice, possibly due to operational issues (equipment costs, limited availability, and poor remuneration) and limited medical education regarding the method. To counter the latter shortcoming, we aspire to provide a pragmatic strategy for interpreting CPET results. Clustering findings of exercise response allows the characterization of patterns that permit the clinician to narrow the list of possible diagnoses rather than pinpointing a specific etiology. We present a proposal for a diagnostic workup and some illustrative cases assessed by CPET. Given that airway hyperresponsiveness and pulmonary vascular disorders, which are within the purview of pulmonology, are common causes of chronic unexplained dyspnea, we also aim to describe the role of bronchial challenge tests and the diagnostic reasoning for investigating the pulmonary circulation in this context.

Quality of life and long-term outcomes after hospitalization for COVID-19: Protocol for a prospective cohort study (Coalition VII). / Qualidade de vida e desfechos em longo prazo após hospitalização por COVID-19: Protocolo para um estudo de coorte prospectivo (Coalizão VII).

INTRODUCTION: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil. METHODS: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include all-cause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals.

INTRODUÇÃO: Os efeitos provocados pela COVID-19 em longo prazo são desconhecidos. O presente estudo tem como objetivo avaliar os fatores associados com a qualidade de vida relacionada à saúde e os desfechos em longo prazo em sobreviventes à hospitalização por COVID-19 no Brasil. MÉTODOS: Este será um estudo multicêntrico de coorte prospectivo, aninhado em cinco ensaios clínicos randomizados desenhados para avaliar os efeitos dos tratamentos específicos para COVID-19 em mais de 50 centros no Brasil. Pacientes adultos sobreviventes à hospitalização por infecção por SARS-CoV-2 comprovada ou suspeita serão seguidos por um período de 1 ano, por meio de entrevistas telefônicas estruturadas. O desfecho primário é o escore de utilidade para qualidade de vida relacionada à saúde após 1 ano, avaliado segundo o questionário EuroQol-5D3L. Os desfechos secundários incluirão mortalidade por todas as causas, eventos cardiovasculares graves, reospitalizações, retorno ao trabalho ou estudo, condição funcional física avaliada pelo instrumento Lawton-Brody Instrumental Activities of Daily Living, dispneia avaliada segundo a escala de dispneia modificada do Medical Research Council, necessidade de suporte ventilatório em longo prazo, sintomas de ansiedade e depressão avaliados segundo a Hospital Anxiety and Depression Scale, sintomas de transtorno de estresse pós-traumático avaliados pela ferramenta Impact of Event Scale-Revised e autoavaliação da condição de saúde, conforme a Escala Visual Analógica do EuroQol-5D3L. Serão utilizadas equações de estimativas generalizada para testar a associação entre cinco conjuntos de variáveis (1 - características demográficas, 2 - condição de saúde pré-morbidade, 3 - características da doença aguda, 4 - terapias específicas para COVID-19 recebidas e 5 - variáveis pós-alta atualizadas) e desfechos. ÉTICA E DISSEMINAÇÃO: O protocolo do estudo foi aprovado pelos Comitês de Ética em Pesquisa de todas as instituições participantes. Os resultados serão disseminados por meio de conferências e periódicos revisados por pares.

Factors associated with mortality in hospitalized patients with newly diagnosed tuberculosis.

The purpose of this study was to identify clinical and epidemiological factors associated with death in patients with an in-hospital diagnosis of tuberculosis (TB), in a city with a high prevalence of TB and human immunodeficiency virus (HIV) infection. The study was a retrospective, cohort study conducted at a general, tertiary-care, university-affiliated hospital. Patients who began treatment for TB after hospitalization were included. Predictors of mortality were assessed. The primary outcomes were the in-hospital mortality and the mortality after discharge. We evaluated the medical records of 311 patients with TB. The overall mortality rate of all study participants was 99/311 (31.8%). The mortality rates during hospitalization and after discharge were 50/311 (16.1%) and 49/261 (18.8%), respectively. Mechanical ventilation, consolidation in chest X-ray, and negative sputum smear were predictors of in-hospital death in multivariate analysis. Independent predictors of mortality after discharge in multivariate analysis included total duration of hospitalization and being a current smoker. We found a high overall mortality rate for patients hospitalized with TB in a region with a high prevalence of TB and HIV. The risk of mortality once patients with TB are hospitalized is unlikely to be explained only by the HIV epidemic.

Protocol implementation for venous thromboembolism prophylaxis: a before-and-after study in medical and surgical patients. / Implementação de protocolo para profilaxia de tromboembolismo venoso: um estudo antes e depois em pacientes clínicos e cirúrgicos.

OBJECTIVE: This study aimed to assess the adequacy of venous thromboembolism (VTE) prophylaxis prescription after a protocol implementation. METHODS: This was a before-and-after study conducted in a tertiary care hospital in Rio Grande do Sul, Southern Brazil. Medical and surgical inpatients aged 18 years or older were assessed for VTE risk and subsequently for thromboprophylaxis adequacy, according to their risk. The evaluations occurred before and after the protocol strategy implementation; it consisted of an online platform to access the protocol, a public posting of the protocol diagram, clinical alerts on the medical staff TV, e-mail alerts, and pop-up alerts on the computerized physician order entry system. The main outcome measure was the adequacy of VTE prophylaxis prescription according to the protocol. RESULTS: A total of 429 patients were evaluated for thromboprophylaxis adequacy (213 before and 216 after). The prevalence of adequacy increased from 54% to 63% (pre and post-intervention, respectively), and after adjustment for patient type and phase of the study, the prevalence ratio reached (PR)=1.20, 95% confidence interval (CI) 1.02-1.42. CONCLUSION: The results showed that the overall appropriateness of thromboprophylaxis prescription was weakly improved. Despite these results, this study provides evidence to date a bunch of strategies for protocol implementations in private institutions in middle-income countries with an open medical staff, as there are few studies investigating these simple and pragmatic interventions.

OBJETIVO: Este estudo visou avaliar a adequação da prescrição de profilaxia de tromboembolismo venoso (TEV) após a implementação do protocolo. MÉTODOS: Trata-se de um estudo antes e depois realizado em um hospital de cuidados terciários no Rio Grande do Sul, Brasil. Pacientes clínicos e cirúrgicos internados, com 18 anos ou mais, foram avaliados para o risco de TEV e, posteriormente, para adequação da tromboprofilaxia, de acordo com o risco. As avaliações ocorreram antes e depois de uma estratégia de implementação de protocolo, que consistiu em uma plataforma on-line para acessar o protocolo, uma postagem pública do diagrama do protocolo, alertas clínicos na sala de convívio médico, alertas de e-mail e alertas pop-up no sistema informatizado de prescrição médica. O Desfecho principal foi a adequação da prescrição de profilaxia do TEV de acordo com o protocolo. RESULTADOS: Foram avaliados 429 pacientes para adequação da tromboprofilaxia (213 antes e 216 depois). A prevalência de adequação aumentou de 54% para 63% (pré e pós-intervenção, respectivamente) e após o ajuste por tipo de paciente e fase do estudo, a razão de prevalência atingiu (RP) = 1,20, intervalo de confiança de 95% (IC) 1,02-1,42. CONCLUSÕES: os resultados mostraram que a adequação geral da prescrição de tromboprofilaxia foi discretamente melhorada. Apesar desses resultados, este estudo fornece evidências, até o momento, de uma série de estratégias para implementar o protocolo em instituições privadas em países de renda média com uma equipe médica aberta, pois há poucas pesquisas investigando esse tipo de intervenção simples e pragmática.

Clinical characteristics and predictors of mechanical ventilation in patients with COVID-19 hospitalized in Southern Brazil. / Características clínicas e preditores de ventilação mecânica em pacientes com COVID-19 hospitalizados no sul do país.

OBJECTIVE: This study aims to describe the clinical characteristics and predictors of mechanical ventilation of adult inpatients with COVID-19 in a single center. METHODS: A retrospective cohort study was performed and included adult inpatients hospitalized from March 17th to May 3rd, 2020, who were diagnosed with SARS-CoV-2 infection. Clinical and demographic characteristics were extracted from electronic medical records. RESULTS: Overall, 88 consecutive patients were included in this study. The median age of the patients was 63 years (IQR 49 - 71); 59 (67%) were male, 65 (86%) had a college degree and 67 (76%) had at least one comorbidity. Twenty-nine (33%) patients were admitted to the intensive care unit, 18 (20%) patients needed mechanical ventilation, and 9 (10.2%) died during hospitalization. The median length of stay in the intensive care unit and the median duration of mechanical ventilation was 23 and 29.5 days, respectively. An age ≥ 65 years was an independent risk factor for mechanical ventilation (OR 8.4 95%CI 1.3 - 55.6 p = 0.02). CONCLUSION: Our findings describe the first wave of Brazilian patients hospitalized for COVID-19. Age was the strongest predictor of respiratory insufficiency and the need for mechanical ventilation in our population.

OBJETIVO: Descrever as características clínicas e os preditores de ventilação mecânica em pacientes adultos internados com COVID-19. MÉTODOS: Conduziu-se um estudo de coorte retrospectiva com inclusão de pacientes hospitalizados entre 17 de março e 3 de maio de 2020, que tiveram o diagnóstico de infecção pelo SARS-CoV-2. As características clínicas e demográficas foram extraídas de registros em prontuário eletrônico. RESULTADOS: Incluíram-se no estudo 88 pacientes consecutivos. A mediana da idade dos pacientes foi de 63 anos (IQR: 49 - 71); 59 (67%) pacientes eram do sexo masculino, 65 (86%) tinham educação universitária e 67 (76%) tinham, no mínimo, uma comorbidade. Dentre eles, 29 (33%) pacientes foram admitidos à unidade de terapia intensiva, 18 (20%) necessitaram de ventilação mecânica e nove (10,2%) morreram durante a hospitalização. O tempo mediano de permanência na unidade de terapia intensiva e o tempo mediano de ventilação mecânica foram, respectivamente, de 23 e 29,5 dias. Idade acima ou igual a 65 anos foi fator de risco independente para ventilação mecânica (RC: 8,4; IC95% de 1,3 - 55,6; valor de p = 0,02). CONCLUSÃO: Nossos achados descrevem a primeira onda de pacientes brasileiros hospitalizados por COVID-19. Em nossa população, idade foi o maior preditor de insuficiência respiratória e necessidade de ventilação mecânica.

Brazilian guidelines for the pharmacological treatment of idiopathic pulmonary fibrosis. Official document of the Brazilian Thoracic Association based on the GRADE methodology.

Idiopathic pulmonary fibrosis (IPF) is a form of chronic interstitial lung disease of unknown cause, which predominantly affects elderly men who are current or former smokers. Even though it is an uncommon disease, it is of great importance because of its severity and poor prognosis. In recent decades, several pharmacological treatment modalities have been investigated for the treatment of this disease, and the classic concepts have therefore been revised. The purpose of these guidelines was to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of IPF in Brazil. We sought to provide guidance on the practical issues faced by clinicians in their daily lives. Patients of interest, Intervention to be studied, Comparison of intervention and Outcome of interest (PICO)-style questions were formulated to address aspects related to the use of corticosteroids, N-acetylcysteine, gastroesophageal reflux medications, endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, pirfenidone, and nintedanib. To formulate the PICO questions, a group of Brazilian specialists working in the area was assembled and an extensive review of the literature on the subject was carried out. Previously published systematic reviews with meta-analyses were analyzed for the strength of the compiled evidence, and, on that basis, recommendations were developed by employing the Grading of Recommendations Assessment, Development and Evaluation approach. The authors believe that the present document represents an important advance to be incorporated in the approach to patients with IPF, aiming mainly to improve its management, and can become an auxiliary tool for defining public policies related to IPF.

Guidelines for the pharmacological treatment of COVID-19. The task-force/consensus guideline of the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases and the Brazilian Society of Pulmonology and Tisiology. / Diretrizes para o tratamento farmacológico da COVID-19. Consenso da Associação de Medicina Intensiva Brasileira, da Sociedade Brasileira de Infectologia e da Sociedade Brasileira de Pneumologia e Tisiologia.

INTRODUCTION: Different therapies are currently used, considered, or proposed for the treatment of COVID-19; for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. METHODS: A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. RESULTS: Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. CONCLUSION: So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients; therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.

Bosentan Inducing Autoimmune Hepatitis in a Patient with Idiopathic Pulmonary Arterial Hypertension.

A 41-year-old woman diagnosed with idiopathic pulmonary hypertension presented symptoms despite the use of vasodilators, requiring treatment with bosentan. Previously, the patient had no signs of autoimmunity and had normal liver function. After three years of bosentan use, aminotransferase levels increased, without improvement after bosentan suspension, leading to complementary investigation. The diagnosis of autoimmune hepatitis was confirmed by biopsy, already in the stage of cirrhosis. In conclusion, in case of aminotransferase levels that remain persistently elevated, despite the reduction in doses and/or suspension of bosentan, autoimmune hepatitis must be investigated and treated urgently due to possibly rapid progression to cirrhosis..

[Indication, access, and use of medicines for chronic respiratory diseases in Brazil: results from the National Survey on Access, Utilization, and Promotion of Rational Use of Medicines in Brazil (PNAUM), 2014]. / Indicação, acesso e utilização de medicamentos para doenças respiratórias crônicas no Brasil: resultados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), 2014.

The study aimed to estimate the prevalence of self-reported chronic respiratory diseases and the indication, access to, and use of medicines, as well as their sources, in the Brazilian adult population. Data were analyzed on adults 20 years and older from the National Survey on Access, Utilization, and Promotion of Rational Use of Medicines in Brazil (PNAUM), conducted from September 2013 to February 2014. Prevalence of chronic respiratory diseases was 3% (95%CI: 2.7-3.3). Of these individuals, 58.1% (95%CI: 51.8-64.0) had an indication for pharmacological treatment. Of those with indication for treatment, 77.1% (95%CI: 71.0-82.8) were using at least one of the prescribed drugs. Total access to therapy was 91.4% (95%CI: 79.9-96.6), and more than half of individuals with chronic respiratory diseases purchased at least one of the drugs in retail pharmacies (57.3%). The most frequently reported drug class was the association of a corticosteroid plus a long-acting beta-2 agonist in inhalation form, the most common example of which was the association budesonide/formoterol (20.3%; 95%CI: 16.0-25.4). According to our study, prevalence of self-reported chronic respiratory diseases was lower than in previous studies published on the Brazilian population. Nearly half of the population reporting chronic respiratory diseases did not have an indication for pharmacological treatment. Among those with such indication, approximately one-fourth were not using medications during the study period, and for those who were on medication, although access was high, they had to pay for their medicines.

O objetivo foi estimar a prevalência de doenças respiratórias crônicas autorreferidas, a indicação, o acesso e o uso de medicamentos, bem como fontes de obtenção, na população adulta brasileira. Foram analisados dados de adultos com idade maior ou igual a 20 anos, provenientes da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), realizada entre setembro de 2013 e fevereiro de 2014. A prevalência de doenças respiratórias crônicas foi de 3% (IC95%: 2,7-3,3). Desses, 58,1% (IC95%: 51,8-64,0) tinham indicação de tratamento farmacológico. Daqueles com indicação de tratamento, 77,1% (IC95%: 71,0-82,8) estavam utilizando pelo menos um dos medicamentos indicados. O acesso total à terapia foi de 91,4% (IC95%: 79,9-96,6), sendo que mais da metade das pessoas com doenças respiratórias crônicas adquiria pelo menos um de seus medicamentos em farmácias comerciais (57,3%). A classe de medicamentos mais referida foi a associação beta-2 agonista de longa duração e corticosteroides sob a forma inalatória, cujo representante mais frequente foi a associação budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acordo com o nosso estudo, a prevalência de doenças respiratórias crônicas autorreferida foi inferior a trabalhos previamente publicados para a população brasileira. Verificou-se que quase metade da população que referiu doenças respiratórias crônicas não tinha indicação de tratamento farmacológico. Já aqueles com indicação, aproximadamente um quarto não utilizava os medicamentos no período do estudo e, para os que usavam, embora o acesso fosse elevado, precisavam pagar para adquirir seus tratamentos.

El objetivo fue estimar la prevalencia de enfermedades respiratorias crónicas autoinformadas, la indicación, el acceso y el uso de medicamentos, así como fuentes de obtención, en población adulta brasileña. Se analizaron datos de adultos con una edad mayor o igual a 20 años, provenientes de la Encuesta Nacional sobre Acceso, Utilización y Promoción del Uso Racional de Medicamentos en Brasil (PNAUM), realizada entre septiembre de 2013 y febrero de 2014. La prevalencia de enfermedades respiratorias crónicas fue de un 3% (IC95%: 2,7-3,3). De estos, un 58,1% (IC95%: 51,8-64,0) tenían indicación de tratamiento farmacológico. De aquellos con indicación de tratamiento, un 77,1% (IC95%: 71,0-82,8) estaban utilizando, por lo menos, uno de los medicamentos indicados. El acceso total a la terapia fue de un 91,4% (IC95%: 79,9-96,6), siendo que más de la mitad de las personas con enfermedades respiratorias crónicas adquiría por lo menos uno de sus medicamentos en farmacias comerciales (57,3%). La clase de medicamentos más referida fue la asociación beta-2 agonista de larga duración y corticosteroides en forma inhalatoria, cuyo representante más frecuente fue la asociación budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acuerdo con nuestro estudio, la prevalencia de enfermedades respiratorias crónicas autoinformada fue inferior a trabajos previamente publicados para la población brasileña. Se verificó que casi la mitad de la población que refirió enfermedades respiratorias crónicas no tenía indicación de tratamiento farmacológico. Ya aquellos que tenían indicación, aproximadamente un cuarto, no utilizaba los medicamentos en el período del estudio y, para los que lo usaban, aunque el acceso fuese elevado, necesitaban pagar para adquirir sus tratamientos.

Impact of impaired pulmonary function on clinical outcomes in survivors of severe COVID-19 without pre-existing respiratory disease / Impacto do comprometimento da função pulmonar nos desfechos clínicos em sobreviventes de COVID-19 grave sem doenças respiratórias preexistentes

ABSTRACT Objective: To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease. Methods: This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities. Results: At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect. Conclusions: The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

RESUMO Objetivo: Investigar o impacto do comprometimento da função pulmonar nos desfechos centrados no paciente após a alta hospitalar em pacientes sem doenças respiratórias preexistentes que foram hospitalizados em virtude de COVID-19 grave. Métodos: Trata-se de um estudo prospectivo de coorte em andamento, no qual pacientes com COVID-19 grave (com idade > 18 anos) são avaliados 2-6 meses depois da alta hospitalar. Avaliamos os sintomas respiratórios, a qualidade de vida relacionada à saúde, a função pulmonar e a distância percorrida no teste de caminhada de seis minutos. A definição de distúrbio ventilatório restritivo foi CPT abaixo do limite inferior da normalidade na pletismografia. As imagens de TC de tórax realizadas durante a hospitalização foram avaliadas quanto à presença e extensão de alterações parenquimatosas. Resultados: Em média 17,2 ± 5,9 semanas depois do diagnóstico de COVID-19, foram avaliados 120 pacientes. Destes, 23 (19,2%) relataram doenças respiratórias crônicas preexistentes e apresentaram pior função pulmonar e maior dispneia aos esforços na consulta de acompanhamento quando comparados aos outros participantes. Quando excluímos os 23 pacientes com doenças respiratórias preexistentes e mais 2 pacientes (sem medidas de volumes pulmonares), observamos distúrbio ventilatório restritivo em 42/95 pacientes (44%). Esse subgrupo de pacientes (52,4% dos quais eram do sexo masculino, com média de idade de 53,9 ± 11,3 anos) apresentou menor eficiência das trocas gasosas (DLCO), maior dispneia na vida diária e dessaturação de oxigênio ao exercício e redução da qualidade de vida relacionada à saúde em comparação com aqueles sem redução da CPT (50,9% dos quais eram do sexo masculino, com média de idade de 58,4 ± 11,3 anos). A necessidade de terapia intensiva e pontuações mais altas no escore de alterações parenquimatosas na TC de tórax apresentaram relação com distúrbio ventilatório restritivo subsequente. Conclusões: A presença de distúrbio ventilatório restritivo aproximadamente 4 meses depois da COVID-19 grave em pacientes sem comorbidades respiratórias prévias implica piores desfechos clínicos.

Usefulness of radiological signs of pulmonary congestion in predicting failed spontaneous breathing trials.

Inspiratory fall in intrathoracic pressure during a spontaneous breathing trial (SBT) may precipitate cardiac dysfunction and acute pulmonary edema. We aimed to determine the relationship between radiological signs of pulmonary congestion prior to an SBT and weaning outcomes. This was a post hoc analysis of a prospective cohort study involving patients in an adult medical-surgical ICU. All enrolled individuals met the eligibility criteria for liberation from mechanical ventilation. Tracheostomized subjects were excluded. The primary endpoint was SBT failure, defined as the inability to tolerate a T-piece trial for 30-120 min. An attending radiologist applied a radiological score on interpretation of digital chest X-rays performed before the SBT. A total of 170 T-piece trials were carried out; SBT failure occurred in 28 trials (16.4%), and 133 subjects (78.3%) were extubated at first attempt. Radiological scores were similar between SBT-failure and SBT-success groups (median [interquartile range] = 3 [2-4] points vs. 3 [2-4] points; p = 0.15), which, according to the score criteria, represented interstitial lung congestion. The analysis of ROC curves demonstrated poor accuracy (area under the curve = 0.58) of chest x-rays findings of congestion prior to the SBT for discriminating between SBT failure and SBT success. No correlation was found between fluid balance in the 48 h preceding the SBT and radiological score results (ρ = -0.13). Radiological findings of pulmonary congestion should not delay SBT indication, given that they did not predict weaning failure in the medical-surgical critically ill population. (ClinicalTrials.gov identifier: NCT02022839 [http://www.clinicaltrials.gov/]).