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Objective: To describe and compare the clinical characteristics and outcomes of patients admitted to intensive care units during the first and second waves of the COVID-19 pandemic. Methods: In this retrospective single-center cohort study, data were retrieved from the Epimed Monitor System; all adult patients admitted to the intensive care unit between March 4, 2020, and October 1, 2021, were included in the study. We compared the clinical characteristics and outcomes of patients admitted to the intensive care unit of a quaternary private hospital in São Paulo, Brazil, during the first (May 1, 2020, to August 31, 2020) and second (March 1, 2021, to June 30, 2021) waves of the COVID-19 pandemic. Results: In total, 1,427 patients with COVID-19 were admitted to the intensive care unit during the first (421 patients) and second (1,006 patients) waves. Compared with the first wave group [median (IQR)], the second wave group was younger [57 (46-70) versus 67 (52-80) years; p<0.001], had a lower SAPS 3 Score [45 (42-52) versus 49 (43-57); p<0.001], lower SOFA Score on intensive care unit admission [3 (1-6) versus 4 (2-6); p=0.018], lower Charlson Comorbidity Index [0 (0-1) versus 1 (0-2); p<0.001], and were less frequently frail (10.4% versus 18.1%; p<0.001). The second wave group used more noninvasive ventilation (81.3% versus 53.4%; p<0.001) and high-flow nasal cannula (63.2% versus 23.0%; p<0.001) during their intensive care unit stay. The intensive care unit (11.3% versus 10.5%; p=0.696) and in-hospital mortality (12.3% versus 12.1%; p=0.998) rates did not differ between both waves. Conclusion: In the first and second waves, patients with severe COVID-19 exhibited similar mortality rates and need for invasive organ support, despite the second wave group being younger and less severely ill at the time of intensive care unit admission. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients., Material and Methods: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life., Results: From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference - 0.65, 95% confidence intervals from -2.95 to 1.36, p = 0.520)., Conclusion: Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020., Gov Identifier: NCT04549922., Competing Interests: Declaration of competing interest None. This study was funded by Ionis Pharmaceutical, US, through a grant provided to HCor. The sponsor reviewed and agreed with the protocol, but had no role in any other aspect of the trial execution. MJ and GB were Ionis employees at the time this study was designed and provided relevant feedback on design of the trial and reviewed the final manuscript for intellectually relevant content. FGZ has received consulting fees from Baxter, unrelated to the scope of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The impact of invasive pulmonary aspergillosis (IPA) on non-neutropenic critically ill patients in intensive care units (ICU) has been demonstrated in recent decades. Furthermore, after the start of the COVID-19 pandemic, COVID-19 associated with pulmonary aspergillosis (CAPA) has become a major concern in ICUs. However, epidemiological data from different regions are scarce. We evaluated the prevalence and clinical-epidemiological data of IPA in patients with COVID-19 requiring mechanical ventilation (MV) in the ICU ("severe COVID-19") and non-COVID ICU patients in MV of a tertiary hospital in the southern region of Brazil. Eighty-seven patients admitted between June 2020 and August 2022 were included; 31 with severe COVID-19. For the diagnosis of IPA or CAPA, algorithms including host factors and mycological criteria (positive culture for Aspergillus spp., immunoassay for galactomannan detection, and/or qPCR) were utilized. The overall incidence of IPA and CAPA in our ICU was 73 cases/1000 ICU hospitalizations. Aspergillosis occurred in 13% (4/31) of the COVID-19 patients, and in 16% (9/56) of the critically ill patients without COVID-19, with mortality rates of 75% (3/4) and 67% (6/9), respectively. Our results highlight the need for physicians enrolled in ICU care to be aware of aspergillosis and for more access of the patients to sensitive and robust diagnostic tests by biomarkers detection., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study investigated the association between the IFITM3 rs12252 polymorphism and the severity and mortality of COVID-19 in hospitalized Brazilian patients. A total of 102 COVID-19 patients were included, and the outcomes of interest were defined as death and the need for mechanical ventilation. Genotypes were assessed using Taqman probes. No significant associations were found between the rs12252 polymorphism and COVID-19 outcomes in the original sample, both for death and the need for mechanical ventilation. A meta-analysis, incorporating previous studies that used death as a severity indicator, revealed no association in the allelic and C-recessive models. However, due to the rarity of the T allele and its absence in the sample, further replication studies in larger and more diverse populations are needed to clarify the role of rs12252 in COVID-19 prognosis.

Introduction: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there was scarce data about clinical/functional conditions during hospitalization or after hospital discharge. Little was known about COVID-19 repercussions and how to do early mobilization in intensive care unit (ICU)., Objective: Identify the time to the initiation of out-of-bed mobilization and the levels of mobility (sitting over the edge of the bed, sitting in a chair, standing, and ambulating) reached by critically ill patients with COVID-19 during hospitalization and the factors that could impact early mobilization., Methods: This was a retrospective observational study of patients with COVID-19 in the ICU., Results: There were 157 surviving COVID-19 patients included in the study (median age: 61 years; median ICU length of stay: 12 days). The median time to initiate out-of-bed mobilization in the ICU was 6 days; between patients who received mechanical ventilation (MV) compared with those who did not, this time was 8 vs. 2.5 days (p < .001). Most patients who used MV were mobilized after extubation (79.6%). During ICU stays, 88.0% of all patients were mobilized out of bed, and 41.0% were able to ambulate either with assistance or independently. The time to initiate out-of-bed mobilization is associated with sedation time and MV time., Conclusion: Despite the pandemic scenario, patients were quickly mobilized out of bed, and most of the patients achieved higher mobility levels in the ICU and at hospital discharge. Sedation time and MV time were associated with delays in initiating mobilization.

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Objectives: During the Coronavirus disease (COVID-19) pandemic, clinicians recommended awake-prone positioning (APP) to avoid the worst outcomes. The objectives of this study were to investigate if APP reduces intubation, death rates, and hospital length of stay (HLOS) in acute COVID-19., Methods: We performed a retrospective cohort with non-mechanically ventilated patients hospitalized in a reference center in Manaus, Brazil, 2020. Participants were stratified into APP and awake-not-prone positioning (ANPP) groups. Also, we conducted a systematic review and performed a meta-analysis to understand if this intervention had different outcomes in resource-limited settings (PROSPERO CRD42023422452)., Results: A total of 115 participants were allocated into the groups. There was no statistical difference between both groups regarding time to intubation (HR: 0.861; 95CI: 0.474-1.1562; p=0.622) and time to death (HR: 1.666; 95CI: 0.939-2.951; p=0.081). APP was not significantly associated with reduced HLOS. A total of 86 articles were included in the systematic review, of which 76 (88,3%) show similar findings after APP. Also, low/middle, and high-income countries were similar regarding such outcomes., Conclusion: APP in COVID-19 does not present clinical improvement that affects mortality, intubation rate and HLOS. The lack of a prone position protocol, obtained through a controlled study, is necessary. After 3 years, APP benefits are still inconclusive.

The COVID-19 pandemic has brought concerns to managers, healthcare professionals, and the general population related to the potential mechanical ventilators' shortage for severely ill patients. In Brazil, there are several initiatives aimed at producing alternative ventilators to cover this gap. To assist the teams that work in these initiatives, we provide a discussion of some basic concepts on physiology and respiratory mechanics, commonly used mechanical ventilation terms, the differences between triggering and cycling, the basic ventilation modes and other relevant aspects, such as mechanisms of ventilator-induced lung injury, respiratory drive, airway heating and humidification, crosscontamination risks, and aerosol dissemination. After the prototype development phase, preclinical benchtests and animal model trials are needed to determine the safety and performance of the ventilator, following the minimum technical requirements. Next, it is mandatory going through the regulatory procedures as required by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA). The manufacturing company should be appropriately registered by ANVISA, which also must be notified about the conduction of clinical trials, following the research protocol approval by the Research Ethics Committee. The registration requisition of the ventilator with ANVISA should include a dossier containing the information described in this paper, which is not intended to cover all related matters but to provide guidance on the required procedures. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to describe practices for weaning from mechanical ventilation (MV), in terms of the use of protocols, methods, and criteria, in pediatric ICUs (PICUs), neonatal ICUs (NICUs), and mixed neonatal/pediatric ICUs (NPICUs) in Brazil. Methods: This was a cross-sectional survey carried out by sending an electronic questionnaire to a total of 298 NICUs, PICUs, and NPICUs throughout Brazil. Results: Completed questionnaires were assessed for 146 hospitals, NICUs accounting for 49.3% of the questionnaires received, whereas PICUs and NPICUs accounted for 35.6% and 15.1%, respectively. Weaning protocols were applied in 57.5% of the units. In the NICUs and NPICUs that used weaning protocols, the method of MV weaning most commonly employed (in 60.5% and 50.0%, respectively) was standardized gradual withdrawal from ventilatory support, whereas that employed in most (53.0%) of the PICUs was spontaneous breathing trial (SBT). During the SBTs, the most common ventilation mode, in all ICUs, was pressure-support ventilation (10.03 ± 3.15 cmH2O) with positive end-expiratory pressure. The mean SBT duration was 35.76 ± 29.03 min in the NICUs, compared with 76.42 ± 41.09 min in the PICUs. The SBT parameters, weaning ventilation modes, and time frame considered for extubation failure were not found to be dependent on the age profile of the ICU population. The findings of the clinical evaluation and arterial blood gas analysis are frequently used as criteria to assess readiness for extubation, regardless of the age group served by the ICU. Conclusions: In Brazil, the clinical practices for weaning from MV and extubation appear to vary depending on the age group served by the ICU. It seems that weaning protocols and SBTs are used mainly in PICUs, whereas gradual withdrawal from ventilatory support is more widely used in NICUs and NPICUs. [ABSTRACT FROM AUTHOR]

Background: Protective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient–ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (VT) at protective levels with NAVA and PSV in patients with ARDS. Methods: We conducted a prospective randomized crossover trial in five ICUs from a university hospital in Brazil and included patients with ARDS transitioning from controlled ventilation to partial ventilatory support. NAVA and PSV were applied in random order, for 15 min each, followed by 3 h in NAVA. Flow, peak airway pressure (Paw) and electrical activity of the diaphragm (EAdi) were captured from the ventilator, and a software (Matlab, Mathworks, USA), automatically detected inspiratory efforts and calculated respiratory rate (RR) and VT. Asynchrony events detection was based on waveform analysis. Results: We randomized 20 patients, but the protocol was interrupted for five (25%) patients for whom we were unable to maintain VT below 6.5 mL/kg in PSV due to strong inspiratory efforts and for one patient for whom we could not detect EAdi signal. For the 14 patients who completed the protocol, VT was 5.8 ± 1.1 mL/kg for NAVA and 5.6 ± 1.0 mL/kg for PSV (p = 0.455) and there were no differences in RR (24 ± 7 for NAVA and 23 ± 7 for PSV, p = 0.661). Paw was greater in NAVA (21 ± 3 cmH2O) than in PSV (19 ± 3 cmH2O, p = 0.001). Most patients were under continuous sedation during the study. NAVA reduced triggering delay compared to PSV (p = 0.020) and the median asynchrony Index was 0.7% (0–2.7) in PSV and 0% (0–2.2) in NAVA (p = 0.6835). Conclusions: It was feasible to keep VT in protective levels with NAVA and PSV for 75% of the patients. NAVA resulted in similar VT, RR and Paw compared to PSV. Our findings suggest that partial ventilatory assistance with NAVA and PSV is feasible as a protective ventilation strategy in selected ARDS patients under continuous sedation. Trial registration ClinicalTrials.gov (NCT01519258). Registered 26 January 2012, https://clinicaltrials.gov/ct2/show/NCT01519258 [ABSTRACT FROM AUTHOR]

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Background : Noninvasive ventilation (NIV) provides positive pressure through different interfaces. A multifunctional full-face mask prototype was developed to provide NIV from three sources: ICU ventilators, portable ventilators, and high-flow medical gas pipeline systems. This study aimed to evaluate the usability of this prototype mask. Methods : This was a quantitative experimental study, conducted in two phases: the development of a full-face mask prototype NIV interface, and the evaluation of its usability by health professionals (evaluators) using a heuristic approach. The Wolf Mask prototype is a multifunctional full-face mask that makes it possible to deliver positive pressure from three different sources: microprocessor-controlled ICU ventilators, portable ventilators with single-limb circuits, and high-flow medical gas. The evaluation was conducted in three stages: presentation of the prototype to the evaluators; skills testing via simulation in a clinical environment; and a review of skills. Results : The prototype was developed by a multidisciplinary team and patented in Brazil. The evaluators were 10 health professionals specializing in NIV. Seven skills related to handling the prototype were evaluated. Three of the ten evaluators called for (non-urgent) changes to improve recognition of the components of the prototype. Only one evaluator called for (non-urgent) changes to improve recognition of the pieces, assembly, and checking the mask. Conclusions : The newly developed multifunctional full-face mask prototype demonstrated excellent usability for providing noninvasive ventilation from multiple sources. Minor modifications may further improve the design.

Objective: To evaluate survival and direct medical costs of patients admitted in private hospitals with COVID-19 during the first wave., Methods: A retrospective, observational study analyzing survival and the economic data retrieved on hospitalized patients with COVID-19. Data from March 2020 to December 2020. The direct cost of hospitalization was estimated using the microcosting method with each individual hospitalization., Results: 342 cases were evaluated. Median age of 61.0 (95% CI 57.0‒65.0). 194 (56.7%) were men. The mortality rate was higher in the female sex (p = 0.0037), ICU (p < 0.001), mechanical ventilation (p<0.001) and elderly groups. 143 (41.8%) patients were admitted to the ICU (95% CI 36.6%-47.1%), of which 60 (41.9%) required MV (95% CI 34.0%-50.0%). Global LOS presented median of 6.7 days (95% CI 6.0-7.2). Mean costs were US$ 7,060,00 (95% CI 5,300.94-8,819,00) for each patient. Mean cost for patients discharged alive and patients deceased was US$ 5,475.53 (95% CI 3,692.91-7,258.14) and US$ 12,955.19 (95% CI 8,106.61-17,803.76), respectively (p < 0.001)., Conclusions: Patients admitted with COVID-19 in these private hospitals point to great economic impact, mainly in the elderly and high-risk patients. It is key to better understand such costs in order to be prepared to make wise decisions during the current and future global health emergencies., Competing Interests: Conflicts of interest The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. There was no financial support., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1βrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patient-ventilator asynchronies are usually detected by visual inspection of ventilator waveforms but with low sensitivity, even when performed by experts in the field. Recently, estimation of the inspiratory muscle pressure (P mus ) waveforms through artificial intelligence algorithm has been proposed (Magnamed®, São Paulo, Brazil). We hypothesized that the display of these waveforms could help healthcare providers identify patient-ventilator asynchronies., Methods: A prospective single-center randomized study with parallel assignment was conducted to assess whether the display of the estimated P mus waveform would improve the correct identification of asynchronies in simulated clinical scenarios. The primary outcome was the mean asynchrony detection rate (sensitivity). Physicians and respiratory therapists who work in intensive care units were randomized to control or intervention group. In both groups, participants analyzed pressure and flow waveforms of 49 different scenarios elaborated using the ASL-5000 lung simulator. In the intervention group the estimated P mus waveform was displayed in addition to pressure and flow waveforms., Results: A total of 98 participants were included, 49 per group. The sensitivity per participant in identifying asynchronies was significantly higher in the P mus group (65.8 ± 16.2 vs. 52.94 ± 8.42, p < 0.001). This effect remained when stratifying asynchronies by type., Conclusions: We showed that the display of the P mus waveform improved the ability of healthcare professionals to recognize patient-ventilator asynchronies by visual inspection of ventilator tracings. These findings require clinical validation., Trial Registration: ClinicalTrials.gov: NTC05144607. Retrospectively registered 3 December 2021., (© 2023. The Author(s).)

Objective: To evaluate whether a model of a daily fitness checklist for spontaneous breathing tests is able to identify predictive variables of extubation failure in pediatric patients admitted to a Brazilian intensive care unit., Methods: This was a single-center, cross-sectional study with prospective data collection. The checklist model comprised 20 items and was applied to assess the ability to perform spontaneous breathing tests., Results: The sample consisted of 126 pediatric patients (85 males (67.5%)) on invasive mechanical ventilation, for whom 1,217 daily assessments were applied at the bedside. The weighted total score of the prediction model showed the highest discriminatory power for the spontaneous breathing test, with sensitivity and specificity indices for fitness failure of 89.7% or success of 84.6%. The cutoff point suggested by the checklist was 8, with a probability of extubation failure less than 5%. Failure increased progressively with increasing score, with a maximum probability of predicting extubation failure of 85%., Conclusion: The extubation failure rate with the use of this model was within what is acceptable in the literature. The daily checklist model for the spontaneous breathing test was able to identify predictive variables of failure in the extubation process in pediatric patients.

Objective: The present study aimed to assess the functional status of children diagnosed with COVID-19 at the time of hospitalization and the associations with clinical features., Methods: This prospective cohort study was carried out with children diagnosed with COVID-19 admitted to a tertiary hospital. The patients' functioning was assessed using the pediatric Functional Status Scale (FSS)., Results: A total of 62 children with a median age of 3 years old were included in the study, and 70% had some comorbidity prior to the diagnosis of COVID-19. The median length of stay was nine days, during which period five patients died. The FSS assessment of the sample showed that approximately 55% had some functional alteration. The group of patients with the highest FSS scores presented a lengthier hospital stay (p = 0.016), required more oxygen therapy (p < 0.001), mechanical ventilation (p = 0.001), and intensive care unit admissions (p = 0.019), and had more cardiac (p = 0.007), neurological (p = 0.003), and respiratory (p = 0.013) comorbidities. In the multivariate analysis, there was an association between the dependent variable length of stay and the total FSS score (b = 0.349, p = 0.004) and the presence of comorbidities (b = 0.357, p = 0.004)., Conclusions: We observed that more than half of the children hospitalized due to COVID-19 had some level of functional change. Greater alterations in functional status were associated with the presence of previous comorbidities, a greater need for ventilatory support, and longer hospital stays.

Background: The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC 2 -SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died., Methods: This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score., Results: From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641-0.944) and 0.704 (95% IC: 0.617-0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001)., Conclusions: The ABC 2 -SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive., (© 2023. The Author(s).)

Objective: To evaluate clinical outcomes and factors associated with mortality, focusing on secondary infections, in critically ill patients with COVID-19 in three Brazilian hospitals during the first pandemic wave., Methods: This was a retrospective observational study involving adult patients with COVID-19 admitted to one of the participating ICUs between March and August of 2020. We analyzed clinical features, comorbidities, source of SARS-CoV-2 infection, laboratory data, microbiology data, complications, and causes of death. We assessed factors associated with in-hospital mortality using logistic regression models., Results: We included 645 patients with a mean age of 61.4 years. Of those, 387 (60.0%) were male, 12.9% (83/643) had undergone solid organ transplant, and almost 10% (59/641) had nosocomial COVID-19 infection. During ICU stay, 359/644 patients (55.7%) required invasive mechanical ventilation, 225 (34.9%) needed renal replacement therapy, 337 (52.2%) received vasopressors, and 216 (33.5%) had hospital-acquired infections (HAIs), mainly caused by multidrug-resistant gram-negative bacteria. HAIs were independently associated with a higher risk of death. The major causes of death were refractory shock and multiple organ dysfunction syndrome but not ARDS, as previously reported in the literature., Conclusions: In this study, most of our cohort required invasive mechanical ventilation and almost one third had HAIs, which were independently associated with a higher risk of death. Other factors related to death were Charlson Comorbidity Index, SOFA score at admission, and clinical complications during ICU stay. Nosocomial COVID-19 infection was not associated with death. The main immediate causes of death were refractory shock and multiple organ dysfunction syndrome.

Background: Capacity strain negatively impacts patient outcome, and the effects of patient surge are a continuous threat during the COVID-19 pandemic. Evaluating changes in mortality over time enables evidence-based resource planning, thus improving patient outcome. Our aim was to describe baseline risk factors associated with mortality among COVID-19 hospitalized patients and to compare mortality rates over time., Methods: We conducted a retrospective cohort study in the largest referral hospital for COVID-19 patients in Sao Paulo, Brazil. We investigated risk factors associated with mortality during hospitalization. Independent variables included age group, sex, the Charlson Comorbidity Index, admission period according to the stage of the first wave of the epidemic (early, peak, and late), and intubation., Results: We included 2949 consecutive COVID-19 patients. 1895 of them were admitted to the ICU, and 1473 required mechanical ventilation. Median length of stay in the ICU was 10 (IQR 5-17) days. Overall mortality rate was 35%, and the adjusted odds ratios for mortality increased with age, male sex, higher Charlson Comorbidity index, need for mechanical ventilation, and being admitted to the hospital during the wave peak of the epidemic. Being admitted to the hospital during the wave peak was associated with a 33% higher risk of mortality., Conclusions: In-hospital mortality was independently affected by the epidemic period. The recognition of modifiable operational variables associated with patient outcome highlights the importance of a preparedness plan and institutional protocols that include evidence-based practices and allocation of resources., Competing Interests: Dr Ferreira received speaker fees from Medtronic, outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The Human Development Index measures a region's development and is a step for development debate beyond the traditional, economic perspective. It can also determine the success of a country's response to the COVID-19 pandemic, mainly affecting the case fatality rate among severe cases of SARS-CoV-2 infection. We aimed to associate the Human Development Index with the case fatality rate due to COVID-19 in each Brazilian state and the Federal District, taking into account comorbidities and the need for invasive mechanical ventilation. We also evaluated the influence of the GINI index, number of intensive care unit beds, and occupied households in subnormal clusters on the case fatality rate. We performed an ecological study including two populations: COVID-19 individuals that did not require the mechanical ventilation protocol; and COVID-19 individuals under invasive mechanical ventilation. We performed a Pearson correlation test and a univariate linear regression analysis on the relationship between Human Development Index, Human Development Index-Education Level, Human Development Index-Life Expectancy, and Human Development Index-Gross National Income per capita and COVID-19 deaths. The same analyses were performed using the other markers. We grouped the patients with COVID-19 according to comorbidities and the need for invasive mechanical ventilation. Alpha = 0.05. We included 848,501 COVID-19 individuals, out of which 153,710 needed invasive mechanical ventilation and 314,164 died, and 280,533 COVID-19 individuals without comorbidity, out of which 33,312 needed invasive mechanical ventilation and 73,723 died. We observed a low negative Pearson correlation between the Human Development Index and death and a moderate negative Pearson correlation between the Human Development Index and deaths of individuals on invasive mechanical ventilation, with or without comorbidity. The univariate linear analysis showed the case fatality rate depends on at least 20-40% of the Human Development Index. In Brazil, regions with a low Human Development Index demonstrated a higher case fatality rate due to COVID-19, mainly in individuals who needed invasive mechanical ventilation, than regions with a higher Human Development Index. Although other indexes studied, such as intensive care unit beds and GINI, were also associated with the COVID-19 case fatality rate, they were not as relevant as the Human Development Index. Brazil is a vast territory comprising cultural, social, and economic diversity, which mirrors the diversity of the Human Development Index. Brazil is a model nation for the study of the Human Development Index's influence on aspects of the COVID-19 pandemic, such as its impact on the case fatality rate.

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Worldwide, transplant programs have suffered a setback during the coronavirus disease 2019 (COVID-19) pandemic and most have temporarily suspended their transplant activities. . We identified 36 liver transplant patients who tested positive for COVID-19. The cases were confirmed by the nucleic acid test (RT-PCR). Epidemiological, demographic, clinical, laboratory, management and outcome data were obtained from the patients' medical records. Fourteen patients (38.9%) required admission to the Intensive Care Unit and/or invasive ventilatory support (severe cases). The mean age of these severe cases was 63.8 years. Regarding the time since the transplant, 71.4% (10/14 patients) had undergone the procedure less than one year before. The immunosuppressive therapy was reduced in patients who required Intensive Care Unit. A total of 12 cases (12/14, 85.7%) required invasive ventilatory support. Eight cases (8/14, 57.1%) required renal replacement therapy. In this group of patients, nine died (64.3 %). In turn, 22 patients had mild to moderate symptoms of COVID-19, not requiring invasive ventilatory support or admission to the Intensive Care Unit. The mean age in these patients was 56.5 years and comorbidities were present in 15 (68.2%) of the cases. In this group, only five patients (5/22, 22.7%) required hospitalization due to complications and there were no deaths This report describes the results of COVID-19 infection in a very specific population, suggesting that liver transplant patients have a significant higher risk of progressing to severeCOVID-19 , with a mortality rate among critically-ill patients above that of the general population.

Objective: To describe clinical characteristics, resource use, outcomes, and to identify predictors of in-hospital mortality of patients with COVID-19 admitted to the intensive care unit., Methods: Retrospective single-center cohort study conducted at a private hospital in São Paulo (SP), Brazil. All consecutive adult (≥18 years) patients admitted to the intensive care unit, between March 4, 2020 and February 28, 2021 were included in this study. Patients were categorized between survivors and non-survivors according to hospital discharge., Results: During the study period, 1,296 patients [median (interquartile range) age: 66 (53-77) years] with COVID-19 were admitted to the intensive care unit. Out of those, 170 (13.6%) died at hospital (non-survivors) and 1,078 (86.4%) were discharged (survivors). Compared to survivors, non-survivors were older [80 (70-88) versus 63 (50-74) years; p<0.001], had a higher Simplified Acute Physiology Score 3 [59 (54-66) versus 47 (42-53) points; p<0.001], and presented comorbidities more frequently. During the intensive care unit stay, 56.6% of patients received noninvasive ventilation, 32.9% received mechanical ventilation, 31.3% used high flow nasal cannula, 11.7% received renal replacement therapy, and 1.5% used extracorporeal membrane oxygenation. Independent predictors of in-hospital mortality included age, Sequential Organ Failure Assessment score, Charlson Comorbidity Index, need for mechanical ventilation, high flow nasal cannula, renal replacement therapy, and extracorporeal membrane oxygenation support., Conclusion: Patients with severe COVID-19 admitted to the intensive care unit exhibited a considerable morbidity and mortality, demanding substantial organ support, and prolonged intensive care unit and hospital stay.

Background: Early reports indicate that AKI is common during COVID-19 infection. Different mortality rates of AKI due to SARS-CoV-2 have been reported, based on the degree of organic dysfunction and varying from public to private hospitals. However, there is a lack of data about AKI among critically ill patients with COVID-19., Methods: We conducted a multicenter cohort study of 424 critically ill adults with severe acute respiratory syndrome (SARS) and AKI, both associated with SARS-CoV-2, admitted to six public ICUs in Brazil. We used multivariable logistic regression to identify risk factors for AKI severity and in-hospital mortality., Results: The average age was 66.42 ± 13.79 years, 90.3% were on mechanical ventilation (MV), 76.6% were at KDIGO stage 3, and 79% underwent hemodialysis. The overall mortality was 90.1%. We found a higher frequency of dialysis (82.7% versus 45.2%), MV (95% versus 47.6%), vasopressors (81.2% versus 35.7%) ( p  < 0.001) and severe AKI (79.3% versus 52.4%; p  = 0.002) in nonsurvivors. MV, vasopressors, dialysis, sepsis-associated AKI, and death ( p  < 0.001) were more frequent in KDIGO 3. Logistic regression for death demonstrated an association with MV (OR = 8.44; CI 3.43-20.74) and vasopressors (OR = 2.93; CI 1.28-6.71; p  < 0.001). Severe AKI and dialysis need were not independent risk factors for death. MV (OR = 2.60; CI 1.23-5.45) and vasopressors (OR = 1.95; CI 1.12-3.99) were also independent risk factors for KDIGO 3 ( p  < 0.001)., Conclusion: Critically ill patients with SARS and AKI due to COVID-19 had high mortality in this cohort. Mortality was largely determined by the need for mechanical ventilation and vasopressors rather than AKI severity.

Background: The novel coronavirus disease-2019 (COVID-19) caused a sudden and unexpected increase in the number of hospital admissions and deaths worldwide. The impact of social distancing on blood stocks was significant. Data on the use of blood products by patients with COVID-19 are scarce., Material and Methods: A retrospective observational study was conducted by analysing the medical records of 3014 hospitalized COVID-19 patients in 16 Brazilian hospitals. Individual data related to clinical, laboratory and transfusion characteristics and outcomes of these patients were collected. Patients characteristics association with mortality and transfusion need were tested independently by logistic regression models., Results: Patients mean age was 57·6 years. In 2298 (76·2%) patients, there was an underlying clinical comorbidity. A total of 1657 (55%) patients required admission to intensive care unit (ICU), and 943 (31%) patients required ventilatory support and orotracheal intubation (OTI). There was a total of 471 (15·6%) deaths among all patients. 325 patients (10·7%) required blood transfusion; 3187 blood products were transfused: 1364 red blood cells in 303 patients, 1092 platelet units in 78 patients, 303 fresh frozen plasma in 49 patients and 423 cryoprecipitates in 21 patients. The mortality among patients who received transfusion was substantially higher than that among the total study population., Conclusion: Need for transfusion was low in COVID-19 patients, but significantly higher in patients admitted to ICU and in those who needed OTI. Knowledge of the transfusion profile of these patients allows better strategies for maintaining the blood stocks of hospitals during the pandemic., (© 2021 International Society of Blood Transfusion.)

Background: Vitamin D acts as a mediator in the immune system regulating antiviral mechanisms and inflammatory processes. Vitamin D insufficiency has been suggested as a potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although its impact on the prognosis of hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear., Objective: This multicenter prospective cohort study was designed to investigate whether serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with hospital length of stay and prognosis in hospitalized patients with COVID-19., Methods: Patients with moderate to severe COVID-19 (n = 220) were recruited from 2 hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and ≥30 ng/mL, and <10 ng/mL and ≥10 ng/mL. The primary outcome was hospital length of stay and the secondary outcomes were the rate of patients who required invasive mechanical ventilation and mortality., Results: There were no significant differences in hospital length of stay when the 4 25(OH)D categories were compared (P = 0.120). Patients exhibiting 25(OH)D <10 ng/mL showed a trend (P = 0.057) for longer hospital length of stay compared with those with 25(OH)D ≥10 ng/mL [9.0 d (95% CI: 6.4, 11.6 d) vs. 7.0 d (95% CI: 6.6, 7.4 d)]. The multivariable Cox proportional hazard models showed no significant associations between 25(OH)D and primary or secondary outcomes., Conclusions: Among hospitalized patients with moderate to severe COVID-19, those with severe 25(OH)D deficiency (<10 ng/mL) exhibited a trend for longer hospital length of stay compared with patients with higher 25(OH)D concentrations. This association was not significant in the multivariable Cox regression model. Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The use of continuous positive airway pressure (CPAP) applied early after birth improves several outcomes when compared with intubation and invasive mechanical ventilation. "Early CPAP" protocols vary in relation to the pressure level, type of interface used, and studied sample., Objective: This study compared intubation rate, exogenous surfactant use, and hospitalization length (among other variables) prior to and after adopting an "early CPAP" protocol in preterm infants with gestational age between 28 and 32 weeks, using intermediate pressures and short binasal prongs., Methods: This was a retrospective study conducted in a public university hospital in Brazil. All preterm infants with gestational age between 28 and 32 weeks were included in the study. The newborns born between January 2011 and December 2012, prior to the protocol being implemented, were considered the historical control group, and those born after implementation, between February 2013 and August 2014 were considered the intervention group., Results: The participants in both groups had similar baseline characteristics (p > 0.05). There were significant reductions in intubation rate (89% versus 73%, p = 0.02), exogenous surfactant use (86% versus 67%, p = 0.02), and median (Q1 - Q3) days of invasive mechanical ventilation [4 (2 - 14) versus 1 (0.15-9), p = 0.01] and length of hospital stay in days [56 (42-77) versus 42 (35-71), p = 0.02]., Conclusions: The findings demonstrate positive outcomes of the early CPAP protocol. This protocol used simple and affordable equipment available in the hospital which could easily be reproduced in other centers, generating better outcomes for preterm infants and reducing hospital expenses., (Copyright © 2021 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: to classify the degree of dependence on nursing care required by children with Congenital Zika Syndrome during hospitalization and to analyze their complexity., Methods: this is a descriptive, observational and quantitative study carried out in a pediatric ward of a public hospital in Rio de Janeiro. Data were collected from hospitalization records between June 2017 and April 2018., Results: 54% of the population studied showed a degree of dependence equivalent to semi-intensive care. On 37.5% of hospitalization days, patients required non-invasive or invasive mechanical ventilation; 31.5% had spontaneous breathing requiring airway clearance by aspiration and/or oxygen therapy., Conclusion: Congenital Zika Syndrome represents a challenge for health professionals due to its uniqueness. In this study, it is expressed by demands for complex and continuous care in hospitalization and in preparation for discharge, requiring semi-intensive nursing care.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19., Methods: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®️) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission., Results: We enrolled 124 patients; 40 were assigned to EPP-AF®️ 400 mg/day, 42 to EPP-AF®️ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03-0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events., Conclusions: Addition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19)., Methods: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality., Results: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints., Conclusions: Administration of NAC in high doses did not affect the evolution of severe COVID-19., Clinical Trials Registration: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To describe the clinical characteristics, laboratory results, imaging findings, and in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals., Methods: A cohort study of laboratory-confirmed COVID-19 patients who were hospitalized from March 2020 to September 2020 in 25 hospitals. Data were collected from medical records using Research Electronic Data Capture (REDCap) tools. A multivariate Poisson regression model was used to assess the risk factors for in-hospital mortality., Results: For a total of 2,054 patients (52.6% male; median age of 58 years), the in-hospital mortality was 22.0%; this rose to 47.6% for those treated in the intensive care unit (ICU). Hypertension (52.9%), diabetes (29.2%), and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation, and 12.1% required kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1%, and acute heart failure in 3.6%. Age >= 65 years, chronic kidney disease, hypertension, C-reactive protein ≥ 100mg/dL, platelet count < 100×10 9 /L, oxygen saturation < 90%, the need for supplemental oxygen, and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%., Conclusions: This study reveals the characteristics and in-hospital outcomes of hospitalized patients with confirmed COVID-19 in Brazil. Certain easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 is a multisystemic disorder that frequently causes acute kidney injury (AKI). However, the precise clinical and biochemical variables associated with AKI progression in patients with severe COVID-19 remain unclear., Methods: We performed a retrospective study on 278 hospitalized patients who were admitted to the ward and intensive care unit (ICU) with COVID-19 between March 2020 and June 2020, at the University Hospital, São Paulo, Brazil. Patients aged ≥ 18 years with COVID-19 confirmed on RT-PCR were included. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We evaluated the incidence of AKI, several clinical variables, medicines used, and outcomes in two sub-groups: COVID-19 patients with AKI (Cov-AKI), and COVID-19 patients without AKI (non-AKI). Univariate and multivariate analyses were performed., Results: First, an elevated incidence of AKI (71.2%) was identified, distributed across different stages of the KDIGO criteria. We further observed higher levels of creatinine, C-reactive protein (CRP), leukocytes, neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) in the Cov-AKI group than in the non-AKI group, at hospital admission. On univariate analysis, Cov-AKI was associated with older age (>62 years), hypertension, CRP, MCV, leucocytes, neutrophils, NLR, combined hydroxychloroquine and azithromycin treatment, use of mechanical ventilation, and vasoactive drugs. Multivariate analysis showed that hypertension and the use of vasoactive drugs were independently associated with a risk of higher AKI in COVID-19 patients. Finally, we preferentially found an altered erythrocyte and leukocyte cellular profile in the Cov-AKI group compared to the non-AKI group, at hospital discharge., Conclusions: In our study, the development of AKI in patients with severe COVID-19 was related to inflammatory blood markers and therapy with hydroxychloroquine/azithromycin, with vasopressor requirement and hypertension considered potential risk factors. Thus, attention to the protocol, hypertension, and some blood markers may help assist doctors with decision-making for the management of COVID-19 patients with AKI., Competing Interests: No authors have competing interests.

Purpose: Clinical characteristics and management of COVID-19 patients have evolved during the pandemic, potentially changing their outcomes. We analyzed the associations of changes in mortality rates with clinical profiles and respiratory support strategies in COVID-19 critically ill patients., Methods: A multicenter cohort of RT-PCR-confirmed COVID-19 patients admitted at 126 Brazilian intensive care units between February 27 th and October 28 th , 2020. Assessing temporal changes in deaths, we identified distinct time periods. We evaluated the association of characteristics and respiratory support strategies with 60-day in-hospital mortality using random-effects multivariable Cox regression with inverse probability weighting., Results: Among the 13,301 confirmed-COVID-19 patients, 60-day in-hospital mortality was 13%. Across four time periods identified, younger patients were progressively more common, non-invasive respiratory support was increasingly used, and the 60-day in-hospital mortality decreased in the last two periods. 4188 patients received advanced respiratory support (non-invasive or invasive), from which 42% underwent only invasive mechanical ventilation, 37% only non-invasive respiratory support and 21% failed non-invasive support and were intubated. After adjusting for organ dysfunction scores and premorbid conditions, we found that younger age, absence of frailty and the use of non-invasive respiratory support (NIRS) as first support strategy were independently associated with improved survival (hazard ratio for NIRS first [95% confidence interval], 0.59 [0.54-0.65], p < 0.001)., Conclusion: Age and mortality rates have declined over the first 8 months of the pandemic. The use of NIRS as the first respiratory support measure was associated with survival, but causal inference is limited by the observational nature of our data.

Introduction: The Coronavirus Disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Data on the mobility level of patients with COVID-19 in the intensive care unit (ICU) are needed., Objective: To describe the mobility level of patients with COVID-19 admitted to the ICU and to address factors associated with mobility level at the time of ICU discharge., Methods: Single center, retrospective cohort study. Consecutive patients admitted to the ICU with confirmed COVID-19 infection were analyzed. The mobility status was assessed by the Perme Score at admission and discharge from ICU with higher scores indicating higher mobility level. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge-ICU admission)/ICU length of stay]. Based on the PMI, patients were divided into two groups: "Improved" (PMI > 0) and "Not improved" (PMI ≤ 0)., Results: A total of 136 patients were included in this analysis. The hospital mortality rate was 16.2%. The Perme Score improved significantly when comparing ICU discharge with ICU admission [20.0 (7-28) points versus 7.0 (0-16) points; P < 0.001]. A total of 88 patients (64.7%) improved their mobility level during ICU stay, and the median PMI of these patients was 1.5 (0.6-3.4). Patients in the improved group had a lower duration of mechanical ventilation [10 (5-14) days versus 15 (8-24) days; P = 0.021], lower hospital length of stay [25 (12-37) days versus 30 (11-48) days; P < 0.001], and lower ICU and hospital mortality rate. Independent predictors for mobility level were lower age, lower Charlson Comorbidity Index, and not having received renal replacement therapy., Conclusion: Patients' mobility level was low at ICU admission; however, most patients improved their mobility level during ICU stay. Risk factors associated with the mobility level were age, comorbidities, and use of renal replacement therapy., Competing Interests: The authors have declared that no competing interests exist.

Purpose: COVID-19 is associated with high morbidity and mortality in patients undergoing surgery. Contrary to elective procedures, emergency operations should not be postponed. We aim to evaluate the profile and outcomes of COVID-19 patients who underwent emergency abdominal surgery., Methods: We performed a retrospective analysis of perioperative data of COVID-19 patients undergoing emergency surgery from April 2020 to August 2020., Results: Eighty-two patients were evaluated due to abdominal complaints, yielding 22 emergency surgeries. The mean APACHE II and SAPS were 18.7 and 68, respectively. Six patients had a PaO 2 /FiO 2 lower than 200 and more than 50% of parenchymal compromise on chest tomography. The most common indications for emergency surgery were hernias (6; 27.2%). The median length of stay was 30 days, and only two patients required reoperation. Postoperatively, 10 (43.3%) patients needed mechanical ventilation for a mean of 6 days. The overall mortality rate was 31.8%., Conclusion: Both postoperative morbidity and mortality are high in COVID-19 patients with respiratory compromise and abdominal emergencies.

Objectives: This study aimed to compare differences in mortality risk factors between admission and follow-up incorporated models., Methods: A retrospective cohort study of 524 patients with confirmed COVID-19 infection admitted to a tertiary medical center in São Paulo, Brazil from 13 March to 30 April 2020. Data were collected on admission, and the third, eighth and fourteenth days of hospitalization. The hazard ratio (HR) was calculated and 28-day in-hospital mortality risk factors were compared between admission and follow-up models using a time-dependent Cox regression model., Results: Of 524 patients, 50.4% needed mechanical ventilation. The 28-day mortality rate was 32.8%. Compared with follow-up, admission models under-estimated the mortality HR for peripheral oxygen saturation <92% (1.21 versus 2.09), heart rate >100 bpm (1.19 versus 2.04), respiratory rate >24/min (1.01 versus 1.82) and mechanical ventilation (1.92 versus 12.93). Low oxygen saturation, higher oxygen support and more biomarkers-including lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea remained associated with mortality after adjustment for clinical factors at follow-up compared with only urea and oxygen support at admission., Conclusions: The inclusion of follow-up measurements changed mortality hazards of clinical signs and biomarkers. Low oxygen saturation, higher oxygen support, lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea could help with prognosis of patients during follow-up., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear., Objective: To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19., Design, Setting, and Participants: This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020., Interventions: Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120)., Main Outcomes and Measures: The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein., Results: Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention., Conclusions and Relevance: Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19., Trial Registration: ClinicalTrials.gov Identifier: NCT04449718.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has highlighted inequalities in access to healthcare systems, increasing racial disparities and worsening health outcomes in these populations. This study analysed the association between sociodemographic characteristics and COVID-19 in-hospital mortality in Brazil., Study Design: A retrospective analysis was conducted on quantitative reverse transcription polymerase chain reaction-confirmed hospitalised adult patients with COVID-19 with a defined outcome (i.e. hospital discharge or death) in Brazil. Data were retrieved from the national surveillance system database (SIVEP-Gripe) between February 16 and August 8, 2020., Methods: Clinical characteristics, sociodemographic variables, use of hospital resources and outcomes of hospitalised adult patients with COVID-19, stratified by self-reported race, were investigated. The primary outcome was in-hospital mortality. The association between self-reported race and in-hospital mortality, after adjusting for clinical characteristics and comorbidities, was evaluated using a logistic regression model., Results: During the study period, Brazil had 3,018,397 confirmed COVID-19 cases and 100,648 deaths. The study population included 228,196 COVID-19-positive adult in-hospital patients with a defined outcome; the median age was 61 years, 57% were men, 35% (79,914) self-reported as Black/Brown and 35.4% (80,853) self-reported as White. The total in-hospital mortality was 37% (85,171/228,196). Black/Brown patients showed higher in-hospital mortality than White patients (42% vs 37%, respectively), were admitted less frequently to the intensive care unit (ICU) (32% vs 36%, respectively) and used more invasive mechanical ventilation (21% vs 19%, respectively), especially outside the ICU (17% vs 11%, respectively). Black/Brown race was independently associated with high in-hospital mortality after adjusting for sex, age, level of education, region of residence and comorbidities (odds ratio = 1.15; 95% confidence interval = 1.09-1.22)., Conclusions: Among hospitalised Brazilian adults with COVID-19, Black/Brown patients showed higher in-hospital mortality, less frequently used hospital resources and had potentially more severe conditions than White patients. Racial disparities in health outcomes and access to health care highlight the need to actively implement strategies to reduce inequities caused by the wider health determinants, ultimately leading to a sustainable change in the health system., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

The new coronavirus disease (COVID-19) is a challenge for clinical decision-making and the effective allocation of healthcare resources. An accurate prognostic assessment is necessary to improve survival of patients, especially in developing countries. This study proposes to predict the risk of developing critical conditions in COVID-19 patients by training multipurpose algorithms. We followed a total of 1040 patients with a positive RT-PCR diagnosis for COVID-19 from a large hospital from São Paulo, Brazil, from March to June 2020, of which 288 (28%) presented a severe prognosis, i.e. Intensive Care Unit (ICU) admission, use of mechanical ventilation or death. We used routinely-collected laboratory, clinical and demographic data to train five machine learning algorithms (artificial neural networks, extra trees, random forests, catboost, and extreme gradient boosting). We used a random sample of 70% of patients to train the algorithms and 30% were left for performance assessment, simulating new unseen data. In order to assess if the algorithms could capture general severe prognostic patterns, each model was trained by combining two out of three outcomes to predict the other. All algorithms presented very high predictive performance (average AUROC of 0.92, sensitivity of 0.92, and specificity of 0.82). The three most important variables for the multipurpose algorithms were ratio of lymphocyte per C-reactive protein, C-reactive protein and Braden Scale. The results highlight the possibility that machine learning algorithms are able to predict unspecific negative COVID-19 outcomes from routinely-collected data.

Background: Very old patients (≥ 80 years-old, VOP) are increasingly admitted to intensive care units (ICUs). Community-acquired pneumonia (CAP) is a common reason for admission and the best strategy of support for respiratory failure in this scenario is not fully known. We evaluated whether noninvasive ventilation (NIV) would be beneficial compared to invasive mechanical ventilation (IMV) regarding hospital mortality., Methods: Multicenter cohort study of VOPs admitted with CAP in need of IMV or NIV to 11 Brazilian ICUs from 2009 through 2012. We used logistic regression models to evaluate the association between the initial ventilatory strategy (NIV vs. IMV) and hospital mortality adjusting for confounding factors. We evaluated effect modification with interaction terms in pre-specified sub-groups., Results: Of 369 VOPs admitted for CAP with respiratory failure, 232 (63%) received NIV and 137 (37%) received IMV as initial ventilatory strategy. IMV patients were sicker at baseline (median SOFA 8 vs. 4). Hospital mortality was 114/232 (49%) for NIV and 90/137 (66%) for IMV. For the comparison NIV vs. IMV (reference), the crude odds ratio (OR) was 0.50 (95% CI, 0.33-0.78, p = 0.002). This association was largely confounded by antecedent characteristics and non-respiratory SOFA (adjOR = 0.70, 95% CI, 0.41-1.20, p = 0.196). The fully adjusted model, additionally including Pao2/Fio2 ratio, pH and Paco2, yielded an adjOR of 0.81 (95% CI, 0.46-1.41, p = 0.452). There was no strong evidence of effect modification among relevant subgroups, such as Pao2/Fio2 ratio ≤ 150 (p = 0.30), acute respiratory acidosis (p = 0.42) and non-respiratory SOFA ≥ 4 (p = 0.53)., Conclusions: NIV was not associated with lower hospital mortality when compared to IMV in critically ill VOP admitted with CAP, but there was no strong signal of harm from its use. The main confounders of this association were both the severity of respiratory dysfunction and of extra-respiratory organ failures., Competing Interests: The authors have declared that no competing interests exist.

Objective: This paper aims to analyze the use of off label (OL) medicines, according to the National Regulatory Agency, in a neonatal intensive care unit of a high-risk maternity hospital in Northeast Brazil., Methods: A cross-sectional study was carried out, using a convenience sample of newborns that used mechanical ventilation at the Intensive Care Unit. As a reference, OL medications were considered for those without an approval for newborn usage by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA) and by the Food and Drugs Administration (FDA)., Results: The sample consisted of 158 newborns, 58.3% male, 87.7% premature, and 70.2% of low or very low birth weight. According to ANVISA, 440 out of the 1,167 prescriptions analyzed were OL, with 98.1% of newborns exposed to at least one of these drugs. According to the FDA, 484 prescriptions were OL, with 75.8% of newborns exposed to at least one of them. Anti-infectives were the most prescribed OL medications. Neonates who presented respiratory failure and pneumonia used these drugs more often; and there was no relation between their use and the number of deaths., Conclusions: Nearly all newborns at the Intensive Care Units, mainly preterm infants, are exposed to at least one off-label (OL) medication during hospital stay, according to the national and international regulatory agencies. No association was found between off-label prescriptions and the frequency of complications or neonatal deaths.

Objective: The purpose of this case report was to describe the role of physical therapists in a neurosurgical center that was converted into a COVID-19 center for critically ill patients., Methods (case Description): On March 16, 2020, the state government of Rio de Janeiro, Brazil, determined that a neurosurgical center with 44 ICU beds equipped with mechanical ventilators should immediately transfer all patients with neurological conditions to other institutions and prepare for patients who were critically ill with COVID-19. The staff, including physical therapists, were trained to handle patients with COVID-19, many of whom were developing acute respiratory distress syndrome (ARDS) with complex and multifactorial ventilatory support needs. Adjustments were made to the physical therapy routine and protocols. Following the stabilization of patients' respiratory condition, physical therapist interventions focused on restoring physical function., Results: A total of 116 confirmed COVID-19 cases were treated from March 17 to May 17, 2020. Sixty percent were men (70) and 40% were women (46), with a median age of 59 years. Eighty-nine percent (103) underwent mechanical ventilation during hospitalization, of which 11% (11) were successfully extubated. Thirty percent (31) of patients underwent tracheostomy, and 26% of those (8) were successfully decannulated. Of the total patients, 57 patients died (mortality rate of 49%), 4 (3%) were transferred to another institution, 23 (20%) were discharged home, and 32 (28%) continued to be hospitalized., Conclusion: Physical therapists in the ICU can facilitate care for critical events such as intubation, patient positioning, ventilatory adjustments, extubation, and functional training., Impact: The coronavirus pandemic has highlighted the importance of physical therapists, specifically in the care of patients who are critically ill with COVID-19. The availability and expertise of physical therapists in the ICU are important for managing critical events such as intubation, patient positioning, ventilatory adjustments, extubation, and functional training., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation., Methods: In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days., Results: Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval - CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group., Conclusion: Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19., Trial Registration: REBEC RBR-949z6v., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Children dependent on invasive home mechanical ventilation (HMV) represent a growing population worldwide. The objective of this study was to assess the experience of 10 years of medical assistance given to pediatric patients on continuous invasive HMV at a Brazilian Home Care Service (HCS), specifically patient characteristics and predictors of outcome (ie, hospital readmission, death, and location of death)., Methods: Medical records for children on invasive HMV at the HCS between 2007 and 2016 were evaluated to collect the following data: age at admission to HCS, sex, principal diagnosis, length of hospital admission and home care period, number and cause of hospital readmissions, number of procedures, death and location of death. The odds ratio was used to understand the likelihood of death for each diagnosis, hospital readmission, and admission age, using a binary logistic regression model., Results: Twenty-seven children were evaluated. The most prevalent diagnosis was cerebral palsy (37.0%). The mean duration of home care was higher than the mean hospital length of stay (955.0 ± 4.6 d versus 341.0 ± 0.5 d, respectively). First hospital readmission mean was at 392.6 ± 548.9 d, and the main cause was respiratory tract infection (45.9%), especially tracheitis. Of the total number of deaths (13), 76.9% occurred in hospital units. There was no statistically significant result observed for greater odds of death for any of the diagnoses and admission age on HCS. However, children who had a hospital readmission < 6 months after hospital discharge presented 10% greater chance of death ( P = .02)., Conclusions: The most prevalent diagnosis of children on continuous invasive HMV was cerebral palsy. The main cause of hospital readmission was respiratory tract infection, especially tracheitis. Having the first hospital readmission at < 6 months after discharge was shown to be a risk factor associated with mortality., Competing Interests: The authors have disclosed on conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.)

Objective: To describe clinical characteristics of pregnant and postpartum women with severe COVID-19 in Brazil and to examine risk factors for mortality., Design: Cross-sectional study based on secondary surveillance database analysis., Setting: Nationwide Brazil., Population or Sample: 978 Brazilian pregnant and postpartum women notified as COVID-19 Acute Respiratory Distress Syndrome (ARDS) cases with complete outcome (death or cure) up to 18 June 2020., Methods: Data was abstracted from the Brazilian ARDS Surveillance System (ARDS-SS) database. All eligible cases were included. Data on demographics, clinical characteristics, intensive care resources use and outcomes were collected. Risk factors for mortality were examined by multivariate logistic regression., Main Outcome Measures: Case fatality rate., Results: We identified 124 maternal deaths, corresponding to a case fatality rate among COVID-19 ARDS cases in the obstetric population of 12.7%. At least one comorbidity was present in 48.4% of fatal cases compared with 24.9% in survival cases. Among women who died, 58.9% were admitted to ICU, 53.2% had invasive ventilation and 29.0% had no respiratory support. The multivariate logistic regression showed that the main risk factors for maternal death by COVID-19 were being postpartum at onset of ARDS, obesity, diabetes and cardiovascular disease, whereas white ethnicity had a protective effect., Conclusions: Negative outcomes of COVID-19 in this population are affected by clinical characteristics but social determinants of health also seem to play a role. It is urgent to reinforce containment measures targeting the obstetric population and ensure high quality care throughout pregnancy and the postpartum period., Tweetable Abstract: A total of 124 COVID-19 maternal deaths were identified in Brazil. Symptoms onset at postpartum and comorbidities are risk factors., (© 2020 John Wiley & Sons Ltd.)

Background: COVID-19 is a rapidly emerging respiratory disease caused by SARS-CoV-2. Due to the rapid human-to-human transmission of SARS-CoV-2, many health care systems are at risk of exceeding their health care capacities, in particular in terms of SARS-CoV-2 tests, hospital and intensive care unit (ICU) beds, and mechanical ventilators. Predictive algorithms could potentially ease the strain on health care systems by identifying those who are most likely to receive a positive SARS-CoV-2 test, be hospitalized, or admitted to the ICU., Objective: The aim of this study is to develop, study, and evaluate clinical predictive models that estimate, using machine learning and based on routinely collected clinical data, which patients are likely to receive a positive SARS-CoV-2 test or require hospitalization or intensive care., Methods: Using a systematic approach to model development and optimization, we trained and compared various types of machine learning models, including logistic regression, neural networks, support vector machines, random forests, and gradient boosting. To evaluate the developed models, we performed a retrospective evaluation on demographic, clinical, and blood analysis data from a cohort of 5644 patients. In addition, we determined which clinical features were predictive to what degree for each of the aforementioned clinical tasks using causal explanations., Results: Our experimental results indicate that our predictive models identified patients that test positive for SARS-CoV-2 a priori at a sensitivity of 75% (95% CI 67%-81%) and a specificity of 49% (95% CI 46%-51%), patients who are SARS-CoV-2 positive that require hospitalization with 0.92 area under the receiver operator characteristic curve (AUC; 95% CI 0.81-0.98), and patients who are SARS-CoV-2 positive that require critical care with 0.98 AUC (95% CI 0.95-1.00)., Conclusions: Our results indicate that predictive models trained on routinely collected clinical data could be used to predict clinical pathways for COVID-19 and, therefore, help inform care and prioritize resources., (©Patrick Schwab, August DuMont Schütte, Benedikt Dietz, Stefan Bauer. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.10.2020.)

Background: Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU., Methods: This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months., Results: The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission., Conclusions: Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality. ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688., Competing Interests: The authors have declared that no competing interests exist.