Clinical and Physiological Variables in Patients with Post-COVID-19 Condition and Persistent Fatigue.

Background/Objectives: Post-COVID-19 condition can manifest through various symptoms such as dyspnea, cognitive disturbances, and fatigue, with mechanisms related to these symptoms, particularly those related to fatigue, still requiring further clarification. Therefore, our aim was to assess the clinical and physiological variables in patients with post-COVID-19 condition and persistent fatigue. Methods: After one year post-COVID-19 infection, the patients underwent a comprehensive evaluation, including a complete blood count, a metabolic panel, complete spirometry, and assessments of dyspnea, quality of life, anxiety and depression, physical capacity, body composition, muscle strength, comorbidities, and medications. The participants were categorized into two groups: G1-fatigue and G2-non-fatigue. Results: Seventy-seven patients (53% female; 55 ± 11.8 years) were included, 37 in G1 and 40 in G2. As for clinical markers and symptoms of illness, in those with persistent fatigue symptoms, a greater sensation of dyspnea [BDI score: 7.5 (6-9) vs. 12 (9-12), p < 0.001; mMRC score: 1 (1-2) vs. 0 (0-1), p = 0.002], worse quality of life [SGRQ total score: 1404 (1007-1897) vs. 497 (274-985); p < 0.001], higher levels of anxiety [HADS-A score: 8 (5-9) vs. 3 (0.5-4); p < 0.001], and a reduction in peripheral and inspiratory muscle strength [handgrip strength: 34 (28-40) vs. 40 (30-46.5) kgf, p = 0.044; MIP: -81 ± 31 vs. -111 ± 33 mmHg, p < 0.001)] were observed. Conclusions: Those with persistent fatigue exhibited a greater sensation of dyspnea, higher levels of anxiety, reduced peripheral and inspiratory muscle strength, and a greater impairment of quality of life. The severity of fatigue was influenced by the worsening quality of life, heightened anxiety levels, and decreased peripheral muscle strength. Additionally, the worse quality of life was associated with a higher sensation of dyspnea, lower muscle strength, and reduced physical capacity.

Long-term oxygen therapy to reduce length of hospital stay in COVID-19.

OBJECTIVE: The aim of this study was to evaluate the efficacy of long-term oxygen therapy as a strategy to reduce hospitalization time in patients affected by COVID-19. METHODS: Between April and December 2021, COVID-19 patients with stable clinical conditions needing supplementary oxygen therapy during hospitalization were oriented to have hospital discharge with long-term oxygen therapy and reassessment after 15 days. RESULTS: A total of 62 patients were evaluated and, 15 days after discharge, 69% of patients had suspended long-term oxygen therapy, with no difference between the groups admitted to the intensive care unit or the ward (p=0.319). Among the individuals who needed to maintain long-term oxygen therapy, in addition to worse P/F ratio (265±57 vs. 345±51; p<0.001) and lower partial pressure of oxygen (55±12 vs. 72±11 mmHg; p<0.001), were those more obese (37±8 vs. 30±6 kg/m2; p=0.032), needed more time for invasive mechanical ventilation (46±27 vs. 20±16 days; p=0.029), had greater persistence of symptoms (p<0.001), and shorter time between the onset of symptoms and the need for hospitalization (7 [2-9] vs. 10 [6-12] days; p=0.039). CONCLUSION: Long-term oxygen therapy is an effective strategy for reducing hospitalization time in COVID-19 patients, regardless of gravity. Additionally, more obese patients with persistence of respiratory symptoms, faster disease evolution, and more days of invasive mechanical ventilation needed to maintain the long-term oxygen therapy longer.

Metal in biological samples from electronic cigarette users and those exposed to their second-hand aerosol: a narrative review.

Introduction: Electronic nicotine delivery systems (ENDS) are gradually becoming more popular, particularly, among today's youth. Despite being marketed as safe by the tobacco industry, the notable absence of regulation in their composition is evident. Both the generated fluids and aerosol exhibit a wide variety of substances that are not yet fully identified. In addition to additives, the aerosol contains metals, the presence of which can be attributed to the excessive heating of metallic filaments used in vaporizing the liquid. Objective: This review aimed to identify and describe studies that have assessed metal levels in biological samples obtained from electronic cigarette users and those exposed to their second-hand aerosol. This involved detailing the types and concentrations of metals identified and the biological samples in which the metals were detected. Methods: Two independent researchers conducted searches in the MEDLINE and EMBASE databases to identify studies that measured the metal levels in human non-invasive biological samples from electronic cigarette users and second-hand exposure. Data were presented as a narrative review. Results: In total, 18 articles were included in this review. Overall active and passive exposure to ENDS was related to higher levels of many metals, including lead and cadmium, in biological samples. ENDS users, in general, have lower metal concentrations in biological samples compared to the users of combustible cigarettes. Conclusion: The exposure to primary and second-hand e-cigarette aerosol is related to higher metal concentrations in the biological samples. The adverse effects of this exposure on long-term users are yet to be determined.

Methylene blue in sepsis and septic shock: a systematic review and meta-analysis.

Background: Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase induced by methylene blue infusion reduces nitric oxide production and improves vasoconstriction. This systematic review and meta-analysis aimed to assess the effects of methylene blue administration compared to placebo on the hemodynamic status and clinical outcomes in patients with sepsis and septic shock. Methods: The authors specifically included randomized controlled trials that compared the use of methylene blue with placebo in adult patients with sepsis and septic shock. The outcomes were length of intensive care unit stay, hemodynamic parameters [vasopressor use], and days on mechanical ventilation. We also evaluated the abnormal levels of methemoglobinemia. This systematic review and meta-analysis were recorded in PROSPERO with the ID CRD42023423470. Results: During the initial search, a total of 1,014 records were identified, out of which 393 were duplicates. Fourteen citations were selected for detailed reading, and three were selected for inclusion. The studies enrolled 141 patients, with 70 of them in the methylene blue group and 71 of them in the control group. Methylene blue treatment was associated with a lower length of intensive care unit stay (MD -1.58; 95%CI -2.97, -0.20; I2 = 25%; p = 0.03), decreased days on mechanical ventilation (MD -0.72; 95%CI -1.26, -0.17; I2 = 0%; p = 0.010), and a shorter time to vasopressor discontinuation (MD -31.49; 95%CI -46.02, -16.96; I2 = 0%; p < 0.0001). No association was found with methemoglobinemia. Conclusion: Administering methylene blue to patients with sepsis and septic shock leads to reduced time to vasopressor discontinuation, length of intensive care unit stay, and days on mechanical ventilation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023423470, CRD42023423470.

Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial.

Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.

Effectiveness of wearing masks during the COVID-19 outbreak in cohort and case-control studies: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. METHODS: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = -0.21 (95% CI, -0.34 to -0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. CONCLUSIONS: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. METHODS: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths. CONCLUSIONS: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

Cardiac function, myocardial fat deposition, and lipid profile in young smokers: a cross-sectional study.

Background: There is a possibility that cardiac morphometric characteristics are associated with the lipid profile, that is, the composition and concentration of triglycerides, total cholesterol, HDL, LDL, and others lipoproteins in young smokers without comorbidities. Thus, this study aimed to evaluate the association of cardiac morphometric characteristics, myocardial fat deposition, and smoking cessation with the lipid profile of young smokers. Methods: A clinical and laboratory evaluation of lipids and the smoking status was performed on 57 individuals, including both a smoker group and a control group. Cardiac magnetic resonance imaging (MRI) with proton spectroscopy was performed to identify cardiac changes and triglyceride (TG) deposition in myocardial tissue. Results: No differences were observed between the groups (control vs. smokers) in relation to the amount of myocardial TG deposition (p = 0.47); however, when TG deposition was correlated with cardiac MRI variables, a positive correlation was identified between smoking history and myocardial TG deposition [hazard ratio (95% CI), 0.07 (0.03-0.12); p = 0.002]. Furthermore, it was observed that the smoking group had lower high-density lipoprotein cholesterol [51 (45.5-59.5) mg/dl vs. 43 (36-49.5) mg/dl, p = 0.003] and higher TG [73 (58-110) mg/dl vs. 122 (73.5-133) mg/dl, p = 0.01] and very-low-density lipoprotein cholesterol [14.6 (11.6-22.2) mg/dl vs. 24.4 (14.7-26.6) mg/dl, p = 0.01] values. In the control and smoking groups, a negative correlation between TGs and the diameter of the aortic root lumen and positive correlation with the thickness of the interventricular septum and end-diastolic volume (EDV) of both the right ventricle (RV) and left ventricle (LV) were noted. Moreover, in the RV, positive correlations with the end-systolic volume (ESV) index (ESVI), stroke volume (SV), ESV, and EDV were observed. Regarding serum free fatty acids, we found a negative correlation between their values and the diameter of the lumen of the ascending aortic vessel. Lipoprotein lipase showed a positive correlation with the SV index of the RV and negative correlation with the diameter of the lumen of the ascending aortic vessel. Conclusion: Several associations were observed regarding cardiac morphometric characteristics, myocardial fat deposition, and smoking cessation with the lipid profile of young smokers.

The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats.

BACKGROUND: Sodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established. OBJECTIVE: To evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM. METHODS: Male Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. STATISTICAL ANALYSIS: ANOVA and Tukey or Kruskal-Wallis and Dunn. RESULTS: DM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM. CONCLUSION: Long-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.

Organizing pneumonia and COVID-19.

Organizing pneumonia (OP) is an interstitial lung disease, and can be cryptogenic, if no cause is identified, or secondary to several conditions. COVID-19-induced persistent inflammation can be associated with interstitial lung disease. We present a review of literature of OP and COVID-19-induced OP with an illustrative case. A 38-year-old man was admitted with COVID-19 that required mechanical ventilation for 56 days. Initial chest computed tomography (CT) revealed diffuse bilateral ground-glass opacities in the lungs with consolidation areas involving 75 % of the parenchyma. After weaning from MV, the patient still required oxygen supplementation. A new chest CT scan also showed extensive diffuse areas of consolidation and ground-glass opacity. OP was hypothesized and 40 mg/day prednisone initiated and continued for six months with resolution of lung functional and image abnormalities. Organizing pneumonia should be included in the differential diagnosis of COVID-19 patients with respiratory symptoms after partial pulmonary recovery.

Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial.

(1) Background: A high concentration of sodium chloride on in vitro cell culture leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of inhaling hypertonic NaCl particles (BREATHOX®) on the duration of COVID-19-induced acute symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX® (2.0 mg NaCl, particles size between 1-10 µm), with five or ten inhalations per day for ten days. The primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened and 98 were randomly assigned to BREATHOX® ten sessions per day (Group 1; 33 patients), BREATHOX® five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up for 28 days. There was an association with cough frequency after 10 days BREATHOX® compared to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06-3.81; Group 2: HR 2.17, 95% CI 1.17-4.04]. No differences between the groups for the reported symptoms' resolution time were seen after 28 days. After combining both BREATHOX® groups, the period to cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, 95% CI 1.20-3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy nose, and dry mouth were considered related to BREATHOX® use and resolved after stopping inhalations. (4) Conclusion: BREATHOX® inhalation is safe and may be effective in reducing the duration of COVID-19-induced coughing.

Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API).

BACKGROUND: Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population. METHODS: Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system. RESULTS: Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged. CONCLUSION: This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

Dual and Poly Use of Tobacco Products in a Sample of Pregnant Smokers: A Cross-sectional Study.

OBJECTIVES: Our aim was to assess the use of dual/poly tobacco in a sample of pregnant women. DESIGN: cross-sectional survey. METHODS: Twenty prenatal care units in Botucatu, Sao Paulo, Brazil. We evaluated 127 high-risk pregnant smokers during prenatal care. Those who were 12-38 weeks pregnant and were currently smoking conventional cigarettes. The study enrollment took place between January 2015 and December 2015. The dual/poly prevalence of tobacco products during pregnancy and the characteristics related to smoking in pregnant smokers through a specific questionnaire containing questions related to sociodemographic characteristics, comorbidities, gestational history, smoking history, secondhand smoke exposure, nicotine dependence, motivation stage and use of alternative forms of tobacco. RESULTS: Mean age was 26.9 ± 6.6 years, most had only elementary education and belonged to lower income economic groups. Twenty-five (19.7%) smoked conventional cigarettes only while 102 used conventional and alternative forms of tobacco products. Smoking pack-years was significantly lower in those only smoking conventional cigarettes than in dual/poly users. Proportion of patients with elevated degree of nicotine dependence was higher in conventional cigarettes users. On the other side, alcohol intake was higher in dual/poly smokers when compared to conventional cigarettes group. The alternative forms of smoking were associated with significantly higher occurrences of comorbidities as pulmonary, cardiovascular and cancer. CONCLUSIONS FOR PRACTICE: The prevalence of alternative forms users of smoking products is high during pregnancy. These data reinforce the importance of a family approach towards smoking in pregnant women and education about the risks of alternative forms of tobacco.

What is Already Known? Studies show that the prevalence of pregnant women who consume alternative forms of tobacco is high, and that these types of smoking are also harmful to pregnancy.What this Study Adds? Our study describes the characteristics related to smoking in pregnant smokers and identifies dual/poly use of tobacco products.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

INTRODUCTION: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. METHODS: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75 years in COPD with initiation of long-acting anti-muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65 years of age. RESULTS: Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65 years preserved an additional 469.7 mL or 236.0 mL, 327.5 mL or 203.3 mL, or 213.5 mL or 137.5 mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65 years of age, respectively. CONCLUSIONS: This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Higher urea-to-albumin ratio is associated with mortality risk in critically ill COVID-19 patients.

BACKGROUND: This study aimed to evaluate the ability of the urea-to-albumin ratio (UAR) to predict mortality in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study included adult patients admitted with COVID-19 at two intensive care units (ICUs) at the University Hospital. Serum urea and albumin concentrations at ICU admission were used to calculate the UAR. All patients were followed up during hospitalization, and the ICU mortality rate was recorded. RESULTS: Two hundred and eleven patients were evaluated. The mean age was 57.8 ± 15.5 years, and 54% were male. Approximately 84.4% of patients were considered to be at nutritional risk by the NRS 2002, and the median UAR was 18.3 (10.5-34.8). The length of stay in the ICU was 10 (6-16) days, 38.4% of the patients required dialysis, and 64.9% died. Age, male sex, need of hemodialysis, lactate level, and inflammatory parameters were associated with higher mortality. Patients non-survivors had a higher UAR (23.7 [13.6-41.8] vs. 10.9 [8.5-16.8]; p < 0.001). The cutoff point with the best performance of UAR in the ROC curve for predicting mortality was ≥12.17 (AUC: 0.7201; CI 95%: 0.656-0.784). Additionally, the risk of mortality was 2.00-fold in the group of patients with UAR ≥12.17 (HR: 2.00 CI: 1.274-3.149; p = 0.003) and remained significant after adjusted analyzes (models 1 and 2). CONCLUSION: Our data suggest that a UAR ≥12.17 increased the risk of mortality by 2.00-fold in critically ill COVID-19 patients.

Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation.

Rationale: Post-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation. Methods: This prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd 90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis. Measurements and main results: 87 patients were evaluated; mean±sd peak oxygen consumption was 19.5±5.0 mL·kg-1·min-1, and the tertiles were ≤17.0, 17.1-22.2 and ≥22.3 mL·kg-1·min-1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg-1·min-1 reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg-1·min-1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption. Conclusions: Exercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association).

Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.