Delirium During Critical Illness and Subsequent Change of Treatment in Patients With Cancer: A Mediation Analysis.

OBJECTIVES: To assess whether delirium during ICU stay is associated with subsequent change in treatment of cancer after discharge. DESIGN: Retrospective cohort study. SETTING: A 50-bed ICU in a dedicated cancer center. PATIENTS: Patients greater than or equal to 18 years old with a previous proposal of cancer treatment (chemotherapy, target therapy, hormone therapy, immunotherapy, radiotherapy, oncologic surgery, and bone marrow transplantation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We considered delirium present if Confusion Assessment Method for the ICU was positive. We assessed the association between delirium and modification of the treatment after discharge. We also performed a mediation analysis to assess both the direct and indirect (i.e., mediated by the development of functional dependence after discharge) of delirium on modification of cancer treatment and whether the modification of cancer treatment was associated with mortality at 1 year. We included 1,134 patients, of whom, 189 (16.7%) had delirium. Delirium was associated with the change in cancer treatment (adjusted odds ratio [OR], 3.80; 95% CI, 2.72-5.35). The association between delirium in ICU and change of treatment was both direct and mediated by the development of functional dependence after discharge. The proportion of the total effect of delirium on change of treatment mediated by the development of functional dependence after discharge was 33.0% (95% CI, 21.7-46.0%). Change in treatment was associated with increased mortality at 1 year (adjusted OR, 2.68; 95% CI, 2.01-3.60). CONCLUSIONS: Patients who had delirium during ICU stay had a higher rate of modification of cancer treatment after discharge. The effect of delirium on change in cancer treatment was only partially mediated by the development of functional dependence after discharge. Change in cancer treatment was associated with increased 1-year mortality.

MiR-200c-3p expression may be associated with worsening of the clinical course of patients with COVID-19.

COVID-19 represents a public health emergency, whose mechanism of which is not fully understood. It is speculated that microRNAs may play a crucial role in host cells after infection by SARS-CoV-2. Thus, our study aimed to analyze the expression of miR-200c-3p in saliva samples from patients with COVID-19. One handred eleven samples from patients with COVID-19 were divided into 4 groups. Group I: 39 patients negative for Covid-19; Group II: 37 positive and symptomatic patients, with no indication of hospitalization; Group III: 21 patients with respiratory disorders (hospitalized); Group IV: 14 patients with severe conditions (oxygen therapy). The expression levels of miR-200c-3p were determined using qPCR. We found greater expression of miR-200c-3p in patients in group IV (p<0.0001), and also verified that patients aged ≥42 years had a higher expression of this miR (p=0.013). Logistic regression analysis revealed that the expression of miR-200c-3p and systemic arterial hypertension are factors independently associated with patients in group IV (p<0.0001). Our results suggest that miR-200c-3p is a predictor of severity independent of COVID-19 risk factors, which could represent a way of screening patients affected by SARS-CoV-2.

Noninvasive ventilation in critically ill very old patients with pneumonia: A multicenter retrospective cohort study.

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.

Awake Prone Positioning in COVID-19 Hypoxemic Respiratory Failure: Exploratory Findings in a Single-center Retrospective Cohort Study.

BACKGROUND: Awake prone positioning has been widely used in patients with COVID-19 respiratory failure to avoid intubation despite limited evidence. Our objective was to evaluate if prone positioning is associated with a reduced intubation rate when compared to usual care. METHODS: This was a retrospective cohort study in the emergency department of a large quaternary hospital in Sao Paulo. We retrieved data from all admitted patients in need of oxygen supplementation (>3 L/min) and tachypnea (>24 ipm) from March 1 to April 30, 2020, excluding those who had any contraindication to the prone position or who had an immediate need for intubation. The primary endpoint was endotracheal intubation up to 15 days. Secondary outcomes included a 6-point clinical outcome ordinal scale, mechanical ventilation-free days, admission to the intensive care unit, and need of hemodialysis and of vasoactive drugs, all assessed at or up to 15 days. We analyzed unadjusted and adjusted effect estimates with Cox proportional hazards models, logistic regression, quantile regression, and sensitivity analyses using propensity score models. RESULTS: Of 925 suspected COVID-19 patients admitted off mechanical ventilation, 166 patients fulfilled inclusion and exclusion criteria: 57 were exposed to prone positioning and 109 to usual care. In the intervention group, 33 (58%) were intubated versus 53 (49%) in the control group. We observed no difference in intubation rates in the univariate analysis (hazard ratio = 1.21, 95% confidence interval [CI] = 0.78 to 1.88, p = 0.39) nor in the adjusted analysis (hazard ratio = 0.90, 95% CI = 0.55 to 1.49, p = 0.69). Results were robust to the sensitivity analyses. Secondary outcomes did not differ between groups. CONCLUSIONS: Awake prone positioning was not associated with lower intubation rates. Caution is necessary before widespread adoption of this technique, pending results of clinical trials.

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol.

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

Ultrasound-Guided Percutaneous Dilational Tracheostomy: A Systematic Review of Randomized Controlled Trials and Meta-Analysis.

INTRODUCTION: Percutaneous dilational tracheostomy (PDT) is a common and increasingly used procedure in the intensive care unit (ICU). It is usually performed with bronchoscopy guidance. Ultrasound has emerged as a useful tool in order to assist PDT, potentially improving its success rate and reducing procedural-related complications. OBJECTIVE: To investigate whether the ultrasound-guided PDT is equivalent or superior to the bronchoscopy-guided or anatomical landmarks-guided PDT with regard to procedural-related and clinical complications. METHODS: A systematic review of randomized clinical trials was conducted comparing an ultrasound-guided PDT to the control groups (either a bronchoscopy-guided PDT or an anatomical landmark-guided PDT) in patients undergoing a PDT in the ICU. The primary outcome was the incidence of major procedural-related and clinical complication rates. The secondary outcome was the incidence of minor complication rates. Random-effect meta-analyzes were used to pool the results. RESULTS: Four studies fulfilled the inclusion criteria and they were analyzed. The studies included 588 participants. There were no differences in the major complication rates between the patients who were assigned to the ultrasound-guided PDT when compared to the control groups (pooled risk ratio [RR]: 0.48; 95% confidence interval [CI]: 0.13-1.71, I2 = 0%). The minor complication rates were not different between the groups, but they had a high heterogeneity (pooled RR: 0.49; 95% CI 0.16-1.50; I2 = 85%). The sensitivity analyzes that only included the randomized controlled trials that used a landmark-guided PDT as the control group showed lower rates of minor complications in the ultrasound-guided PDT group (pooled RR: 0.55; 95% CI: 0.31-0.98, I2 = 0%). CONCLUSION: The ultrasound-guided PDT seems to be safe and it is comparable to the bronchoscopy-guided PDT regarding the major and minor procedural-related or clinical complications. It also seems to reduce the minor complications when compared to the anatomical landmark-guided PDT.

Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil - study protocol

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

ICU staffing feature phenotypes and their relationship with patients' outcomes: an unsupervised machine learning analysis.

PURPOSE: To study whether ICU staffing features are associated with improved hospital mortality, ICU length of stay (LOS) and duration of mechanical ventilation (MV) using cluster analysis directed by machine learning. METHODS: The following variables were included in the analysis: average bed to nurse, physiotherapist and physician ratios, presence of 24/7 board-certified intensivists and dedicated pharmacists in the ICU, and nurse and physiotherapist autonomy scores. Clusters were defined using the partition around medoids method. We assessed the association between clusters and hospital mortality using logistic regression and with ICU LOS and MV duration using competing risk regression. RESULTS: Analysis included data from 129,680 patients admitted to 93 ICUs (2014-2015). Three clusters were identified. The features distinguishing between the clusters were: the presence of board-certified intensivists in the ICU 24/7 (present in Cluster 3), dedicated pharmacists (present in Clusters 2 and 3) and the extent of nurse autonomy (which increased from Clusters 1 to 3). The patients in Cluster 3 exhibited the best outcomes, with lower adjusted hospital mortality [odds ratio 0.92 (95% confidence interval (CI), 0.87-0.98)], shorter ICU LOS [subhazard ratio (SHR) for patients surviving to ICU discharge 1.24 (95% CI 1.22-1.26)] and shorter durations of MV [SHR for undergoing extubation 1.61(95% CI 1.54-1.69)]. Cluster 1 had the worst outcomes. CONCLUSION: Patients treated in ICUs combining 24/7 expert intensivist coverage, a dedicated pharmacist and nurses with greater autonomy had the best outcomes. All of these features represent achievable targets that should be considered by policy makers with an interest in promoting equal and optimal ICU care.

Ultrasound-guided percutaneous dilational tracheostomy versus bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients (TRACHUS): a randomized noninferiority controlled trial.

PURPOSE: Percutaneous dilational tracheostomy (PDT) is routinely performed in the intensive care unit with bronchoscopy guidance. Recently, ultrasound has emerged as a potentially useful tool to assist PDT and reduce procedure-related complications. METHODS: An open-label, parallel, non-inferiority randomized controlled trial was conducted comparing an ultrasound-guided PDT with a bronchoscopy-guided PDT in mechanically ventilated critically ill patients. The primary outcome was procedure failure, defined as a composite end-point of conversion to a surgical tracheostomy, unplanned associated use of bronchoscopy or ultrasound during PDT, or the occurrence of a major complication. RESULTS: A total of 4965 patients were assessed for eligibility. Of these, 171 patients were eligible and 118 underwent the procedure, with 60 patients randomly assigned to the ultrasound group and 58 patients to the bronchoscopy group. Procedure failure occurred in one (1.7%) patient in the ultrasound group and one (1.7%) patient in the bronchoscopy group, with no absolute risk difference between the groups (90% confidence interval, -5.57 to 5.85), in the "as treated" analysis, not including the prespecified margin of 6% for noninferiority. No other patient had any major complication in either group. Procedure-related minor complications occurred in 20 (33.3%) patients in the ultrasound group and in 12 (20.7%) patients in the bronchoscopy group (P = 0.122). The median procedure length was 11 [7-19] vs. 13 [8-20] min (P = 0.468), respectively, and the clinical outcomes were also not different between the groups. CONCLUSIONS: Ultrasound-guided PDT is noninferior to bronchoscopy-guided PDT in mechanically ventilated critically ill patients.

One-year survival and resource use after critical illness: impact of organ failure and residual organ dysfunction in a cohort study in Brazil.

INTRODUCTION: In this study, we evaluated the impacts of organ failure and residual dysfunction on 1-year survival and health care resource use using Intensive Care Unit (ICU) discharge as the starting point. METHODS: We conducted a historical cohort study, including all adult patients discharged alive after at least 72 h of ICU stay in a tertiary teaching hospital in Brazil. The starting point of follow-up was ICU discharge. Organ failure was defined as a value of 3 or 4 in its corresponding component of the Sequential Organ Failure Assessment score, and residual organ dysfunction was defined as a score of 1 or 2. We fit a multivariate flexible Cox model to predict 1-year survival. RESULTS: We analyzed 690 patients. Mortality at 1 year after discharge was 27%. Using multivariate modeling, age, chronic obstructive pulmonary disease, cancer, organ dysfunctions and albumin at ICU discharge were the main determinants of 1-year survival. Age and organ failure were non-linearly associated with survival, and the impact of organ failure diminished over time. We conducted a subset analysis with 561 patients (81%) discharged without organ failure within the previous 24 h of discharge, and the number of residual organs in dysfunction remained strongly associated with reduced 1-year survival. The use of health care resources among hospital survivors was substantial within 1 year: 40% of the patients were rehospitalized, 52% visited the emergency department, 90% were seen at the outpatient clinic, 14% attended rehabilitation outpatient services, 11% were followed by the psychological or psychiatric service and 7% used the day hospital facility. Use of health care resources up to 30 days after hospital discharge was associated with the number of organs in dysfunction at ICU discharge. CONCLUSIONS: Organ failure was an important determinant of 1-year outcome of critically ill survivors. Nevertheless, the impact of organ failure tended to diminish over time. Resource use after critical illness was elevated among ICU survivors, and a targeted action is needed to deliver appropriate care and to reduce the late critical illness burden.