Association between piperacillin/tazobactam use and acute kidney injury in critically ill patients: a retrospective multicentre cohort study.

BACKGROUND: Piperacillin/tazobactam is one of the most common antibiotics prescribed in the ICU and the combination of piperacillin/tazobactam with vancomycin has been associated with acute kidney injury (AKI) in critically ill patients. However, data on the risk of AKI with piperacillin/tazobactam, despite vancomycin co-exposure, are lacking. OBJECTIVES: To investigate the association of piperacillin/tazobactam with AKI and renal replacement therapy (RRT) among adult ICU patients. METHODS: We analysed data from patients included in two open access databases (MIMIC-IV and eICU). Critically ill patients who received piperacillin/tazobactam or cefepime (a cephalosporin with similar broad-spectrum activity to piperacillin/tazobactam) during their first ICU stay were eligible for the study. Marginal structural Cox models, accounting for time-fixed covariates and time-dependent covariates were performed. The primary outcomes were AKI and need of RRT. RESULTS: A total of 20 107 patients were included, with 11 213 in the piperacillin/tazobactam group and 8894 in the cefepime group. Exposure to piperacillin/tazobactam was associated with AKI (HR 1.77; 95% CI 1.51-2.07; P < 0.001) and with need of RRT (HR 1.31; 95% CI 1.08-1.57; P = 0.005). Tests for interaction were not statistically significant for occurrence of AKI and RRT in the subgroup of patients exposed to vancomycin or not (P = 0.26 and P = 0.6, respectively). CONCLUSIONS: In critically ill patients, exposure to piperacillin/tazobactam was associated with increased risk of AKI and with increased risk of RRT, regardless of combination therapy with vancomycin.

Adverse events leading to intensive care unit admission in a low-and-middle-income-country: A prospective cohort study and a systematic review.

INTRODUCTION: Adverse events (AE) are frequent in critical care and could be even more prevalent in LMIC due to a shortage of ICU beds and Human resources. There is limited data on how relevant AE are among the reasons for ICU admission, being all of which published by High-Income-Countries services. Our main goal is to describe the rate of adverse events-related ICU admissions and their preventability in a LMIC scenario, comparing our results with previous data. METHODS: This was a prospective cohort study, during a one-year period, in two general ICUs from a tertiary public academic hospital. Our exposure of interest was ICU admission related to an AE in adult patients, we further characterized their preventability and clinical outcomes. We also performed a systematic review to identify and compare previous published data on ICU admissions due to AE. RESULTS: Among all ICU admissions, 12.1% were related to an AE (9.8% caused by an AE, 2.3% related but not directly caused by an AE). These ICU admissions were not associated with a higher risk of death, but most of them were potentially preventable (70.9% of preventability rate, representing 8.6% of all ICU admissions). The meta-analysis resulted in a proportion of ICU admissions due to AE of 11% (95% CI 6%-16%), with a preventability rate of 54% (95% CI 42%-66%). CONCLUSIONS: In this prospective cohort, adverse events were a relevant reason for ICU admission. This result is consistent with data retrieved from non-LMIC as shown in our meta-analysis. The high preventability rate described reinforces that quality and safety programs could work as a tool to optimize scarce resources.

Ninety-day outcomes in patients diagnosed with COVID-19 in São Paulo, Brazil: a cohort study.

OBJECTIVE: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. METHODS: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. RESULTS: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. CONCLUSIONS: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Twelve Months and Counting: Following Clinical Outcomes in Critical COVID-19 Survivors.

Rationale: Recent reports suggest that patients with severe coronavirus disease (COVID-19) often experience long-term consequences of the infection. However, studies on intensive care unit (ICU) survivors are underrepresented. Objectives: We aimed to explore 12-month clinical outcomes after critical COVID-19, describing the longitudinal progress of disabilities, frailty status, frequency of cognitive impairment, and clinical events (rehospitalization, institutionalization, and falls). Methods: We performed a prospective cohort study of survivors of COVID-19 ICU admissions in Sao Paulo, Brazil. We assessed patients every 3 months for 1 year after hospital discharge and obtained information on 15 activities of daily living (basic, instrumental, and mobility activities), frailty, cognition, and clinical events. Results: We included 428 patients (mean age of 64 yr, 61% required invasive mechanical ventilation during ICU stay). The number of disabilities peaked at 3 months compared with the pre-COVID-19 period (mean difference, 2.46; 99% confidence interval, 1.94-2.99) and then decreased at 12 months (mean difference, 0.67; 99% confidence interval, 0.28-1.07). At 12-month follow-up, 12% of patients were frail, but half of them presented frailty only after COVID-19. The prevalence of cognitive symptoms was 17% at 3 months and progressively decreased to 12.1% (P = 0.012 for trend) at the end of 1 year. Clinical events occurred in all assessments. Conclusions: Although a higher burden of disabilities and cognitive symptoms occurred 3 months after hospital discharge of critical COVID-19 survivors, a significant improvement occurred during the 1-year follow-up. However, one-third of the patients remained in worse conditions than their pre-COVID-19 status.

Ninety-day outcomes in patients diagnosed with COVID-19 in São Paulo, Brazil: a cohort study / Desfechos em 90 dias entre pacientes com diagnóstico de COVID-19 em São Paulo (SP): estudo de coorte

ABSTRACT Objective: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. Methods: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. Results: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. Conclusions: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

RESUMO Objetivo: A COVID-19 tem sido associada a um fardo significativo para aqueles que sobrevivem à fase aguda. Nosso objetivo foi descrever a qualidade de vida e sintomas de ansiedade, depressão e transtorno de estresse pós-traumático (TEPT) 90 dias após a alta hospitalar em pacientes com COVID-19. Métodos: Pacientes com COVID-19 internados em um hospital privado na cidade de São Paulo (SP) entre abril de 2020 e abril de 2021 foram entrevistados por telefone 30 e 90 dias após a alta para avaliar a qualidade de vida e sintomas de depressão, ansiedade e TEPT. Resultados: Foram incluídos 2.138 pacientes. A média de idade foi de 58,6 ± 15,8 anos, e a mediana do tempo de internação hospitalar foi de 9,0 (5,0-15,8) dias. Entre os dois momentos, a depressão aumentou de 3,1% para 7,2% (p < 0,001), a ansiedade, de 3,2% para 6,2% (p < 0,001), e o TEPT, de 2,3% para 5,0% (p < 0,001). Pelo menos um sintoma físico relacionado ao diagnóstico de COVID-19 persistia em 32% dos pacientes no 90º dia. Conclusões: A persistência dos sintomas físicos foi elevada mesmo 90 dias após a alta. Embora a prevalência de sintomas de ansiedade, depressão e TEPT tenha sido baixa, esses sintomas persistiram por três meses, com aumento significativo entre os momentos. Esse achado indica a necessidade de identificar os pacientes de risco para que possam receber o encaminhamento adequado no momento da alta.

Effects of an educational intervention for rational cardiac enzyme requisitions in critically ill patients: a pre-post intervention study.

BACKGROUND: Although cardiac troponin is recommended as the biomarker of choice to evaluate myocardial injury, inappropriate low-value ordering practice is frequent, particularly routine ordering of creatine kinase-myocardial band (CK-MB) tests where troponin is available. OBJECTIVE: The aim of this study was to evaluate the impact of an educational intervention for rational request of cardiac biomarkers in the intensive care unit. METHOD: We conducted a quasi-experimental, pre-post implementation study of an educational program (expository-dialogue presentation and disclosure of a decision algorithm) for rational cardiac biomarker testing in adult critically ill patients. The study was divided into two 12-month periods: pre-intervention (September 2017-August 2018) and post-intervention (October 2018-September 2019). An interrupted time series with a segmented regression model was applied to analyze variation over time in CK-MB and troponin testing. RESULTS: We included 4429 patients: 2181 patients in the pre-intervention period and 2248 patients in the post-intervention period. A reduction in the concomitance of CK-MB and troponin testing was observed (concomitance in 1415 tests in the pre-intervention period vs 348 tests in the post-intervention period). The interrupted time series analysis demonstrated a noticeable immediate reduction in the concomitance of CK-MB with troponin after the intervention (-0.13 tests per patient, P = 0.0016) but not in the secular trend for the concomitance. The proportion of patients with the acute coronary syndrome as a discharge diagnosis was not different between the pre- and post-intervention period. CONCLUSION: Our pre-post interventional study demonstrated a significant decrease in the concomitance of CK-MB and troponin tests. A rational high-value ordering practice of cardiac biomarkers is possible in critically ill patients and might be suitable for educational interventions.

Evaluation of eleven immunochromatographic assays for SARS-CoV-2 detection: investigating the dengue cross-reaction.

COVID-19 disease is spread worldwide and diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and a low-cost alternative especially in low and middle-income countries, which lack structure to perform certain diagnostic techniques. Here we evaluate the sensitivity and specificity of eleven different IC tests in 145 serum samples from confirmed cases of COVID-19 using RT-PCR and 100 negative serum samples from blood donors collected in February 2019. We also evaluated the cross-reactivity with dengue using 20 serum samples from patients with confirmed diagnosis for dengue collected in early 2019 through four different tests. We found high sensitivity (92%), specificity (100%) and an almost perfect agreement (Kappa 0.92) of IC assay, especially when we evaluated IgG and IgM combined after 10 days from the onset of symptoms with RT-PCR. However, we detected cross-reactivity between dengue and COVID-19 mainly with IgM antibodies (5 to 20% of cross-reaction) and demonstrated the need for better studies about diagnostic techniques for these diseases.

Comparison of the accuracy of residents, senior physicians and surrogate decision-makers for predicting hospital mortality of critically ill patients. / Comparação da acurácia de residentes, médicos seniores e decisores substitutos na previsão da mortalidade hospitalar de pacientes críticos.

OBJECTIVE: To compare the predictive performance of residents, senior intensive care unit physicians and surrogates early during intensive care unit stays and to evaluate whether different presentations of prognostic data (probability of survival versus probability of death) influenced their performance. METHODS: We questioned surrogates and physicians in charge of critically ill patients during the first 48 hours of intensive care unit admission on the patient's probability of hospital outcome. The question framing (i.e., probability of survival versus probability of death during hospitalization) was randomized. To evaluate the predictive performance, we compared the areas under the ROC curves (AUCs) for hospital outcome between surrogates and physicians' categories. We also stratified the results according to randomized question framing. RESULTS: We interviewed surrogates and physicians on the hospital outcomes of 118 patients. The predictive performance of surrogate decisionmakers was significantly lower than that of physicians (AUC of 0.63 for surrogates, 0.82 for residents, 0.80 for intensive care unit fellows and 0.81 for intensive care unit senior physicians). There was no increase in predictive performance related to physicians' experience (i.e., senior physicians did not predict outcomes better than junior physicians). Surrogate decisionmakers worsened their prediction performance when they were asked about probability of death instead of probability of survival, but there was no difference for physicians. CONCLUSION: Different predictive performance was observed when comparing surrogate decision-makers and physicians, with no effect of experience on health care professionals' prediction. Question framing affected the predictive performance of surrogates but not of physicians.

OBJETIVO: Comparar o desempenho preditivo de residentes, médicos seniores de unidades de terapia intensiva e decisores substitutos dos pacientes logo no início da internação na unidade de terapia intensiva e avaliar se diferentes apresentações de prognóstico (probabilidade de sobrevida versus probabilidade de óbito) influenciaram seus desempenhos. MÉTODOS: Os decisores substitutos e os médicos responsáveis pelos pacientes críticos foram questionados durante as primeiras 48 horas de internação na unidade de terapia intensiva sobre a probabilidade do desfecho hospitalar do paciente. O enquadramento da pergunta (isto é, a probabilidade de sobrevida versus a probabilidade de óbito durante a internação) foi randomizado. Para avaliar o desempenho preditivo, comparou-se a área sob a curva ROC para desfecho hospitalar entre as categorias decisores substitutos e médicos. Também estratificaram-se os resultados de acordo com o enquadramento da pergunta randomizado. RESULTADOS: Entrevistaram-se decisores substitutos e médicos sobre os desfechos hospitalares de 118 pacientes. O desempenho preditivo dos decisores substitutos foi significativamente inferior ao dos médicos (área sob a curva de 0,63 para decisores substitutos, 0,82 para residentes, 0,80 para residentes de medicina intensiva e 0,81 para médicos seniores de unidade de terapia intensiva). Não houve aumento no desempenho preditivo quanto à experiência dos médicos (ou seja, médicos seniores não previram desfechos melhor que médicos juniores). Os decisores substitutos pioraram seu desempenho de previsão quando perguntados sobre a probabilidade de óbito ao invés da probabilidade de sobrevida, mas não houve diferença entre os médicos. CONCLUSÃO: Observou-se desempenho preditivo diferente ao comparar decisores substitutos e médicos, sem qualquer efeito da experiência no prognóstico dos profissionais de saúde. O enquadramento da pergunta afetou o desempenho preditivo dos substitutos, mas não o dos médicos.

Performance of NUTRIC score to predict 28-day mortality in critically ill patients after replacing APACHE II with SAPS 3.

OBJECTIVES: The Nutrition Risk in the Critically Ill (NUTRIC) score has been advocated as a screening tool for nutrition risk assessment in critically ill patients. It was developed and validated to predict 28-day mortality using Acute Physiology and Chronic Health Evaluation II (APACHE II) score as one of its components. However, nowadays the Simplified Acute Physiology Score 3 (SAPS 3) demonstrates better performance. We aimed to test the performance of NUTRIC score in predicting 28-day mortality after replacement of APACHE II by SAPS 3, and the interaction between nutrition adequacy and mortality. METHODS: Adult patients who received nutrition therapy and remained >3 days in intensive care unit were retrospectively evaluated. In order to replace APACHE II component, we used ranges of SAPS 3 with similar predicted mortality. Discrimination between these tools in predicting 28-day mortality was assessed using the ROC curve, calibration was evaluated with calibration belt, and correlation with intraclass correlation. The relationship between nutritional adequacy and mortality was assessed in a subgroup with available data. RESULTS: 542 patients were analyzed (median age of 78 years old, 73.4% admitted for non-surgical reasons and 28-day mortality was 18.1%). Mortality prediction discrimination did not differ between tools (p>0.05), but showed a good agreement (intraclass correlation 0.86) with good calibration. In the subgroup analysis for nutritional adequacy (n = 99), no association with mortality was observed. CONCLUSION: Performance of NUTRIC score with SAPS 3 is similar to the original tool. Therefore, it might be used in settings where APACHE II is not available.

Phenotypes of sickle cell intensive care admissions: an unsupervised machine learning approach in a single-center retrospective cohort.

Sickle cell disease (SCD) is associated with multiple known complications and increased mortality. This study aims to further understand the profile of intensive care unit (ICU) admissions of SCD patients. In this single-center retrospective cohort (approval number 0926-11), we evaluated SCD-related ICU admissions at our hospital in São Paulo, Brazil. Admissions were clustered using clinical data and organ dysfunction at ICU admission. A hierarchical clustering method was used to distinguish phenotypes. From 140 admissions obtained, 125 were included. The mean age was 30 years, 48% were male, and SS genotype was predominant (71.2%). Non-surgical causes of admissions accounted for 85.6% (n = 107). The mean Sequential Organ Failure Assessment score (SOFA) was 4 (IQR 2-7). Vasopressors were required by 12% and mechanical ventilation by 17.6%. After analysis of the average silhouette width, the optimal number of clusters was 3: cluster 1 (n = 69), cluster 2 (n = 25), cluster 3 (n = 31). Cluster 1 had a mean age of 29 years, 87% of SS genotype, and mean SOFA of 4. Cluster 2 had a mean age of 37 years, 80% of SS genotype, and mean SOFA of 8. Cluster 3 had a mean age of 26 years, 29% of SS genotype, and mean SOFA of 3. The need for mechanical ventilation was 11.6%, 44%, and 9.7%, respectively. Mortality was significantly higher in cluster 2 (44%, p = 0.012). This cohort of critical SCD admissions suggested the presence of three different profiles. This can be informative in the ICU setting to identify SCD patients at higher risk of worse outcomes.

Association of Frailty, Organ Support, and Long-Term Survival in Critically Ill Patients With COVID-19.

Few studies have explored the effect of frailty on the long-term survival of COVID-19 patients after ICU admission. Furthermore, the Clinical Frailty Scale (CFS) validity in critical care patients remains debated. We investigated the association between frailty and 6-month survival in critically ill COVID-19 patients. We also explored whether ICU resource utilization varied according to frailty status and examined the concurrent validity of the CFS in this setting. DESIGN: Ancillary study of a longitudinal prospective cohort. SETTING: University hospital in São Paulo. PATIENTS: Patients with severe COVID-19 admitted to ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed baseline frailty using the CFS (1-9; frail ≥ 5) and used validated procedures to compute a Frailty Index (0-1; frail > 0.25). We used Cox models to estimate associations of frailty status with 6-month survival after ICU admission and area under the receiver operating characteristic curves (AUCs) to estimate CFS's accuracy in identifying frailty according to Frailty Index. We included 1,028 patients (mean age, 66 yr; male, 61%). Overall, 224 (22%) patients were frail (CFS ≥ 5), and 608 (59%) died over the 6-month follow-up. Frailty was independently associated with lower 6-month survival and further stratified mortality in patients with similar age and Sequential Organ Failure Assessment scores. We additionally verified that the CFS was highly accurate in identifying frailty as defined by the Frailty Index (AUC, 0.91; 95% CI, 0.89-0.93). Although treatment modalities did not diverge according to frailty status, higher CFS scores were associated with withholding organ support due to refractory organ failure. CONCLUSIONS: One in five COVID-19 patients admitted to the ICU was frail. CFS scores greater than or equal to 5 were associated with lower long-term survival and decisions on withholding further escalation of invasive support for multiple organ failure in the ICU. Clinicians should consider frailty alongside sociodemographic and clinical measures to have a fuller picture of COVID-19 prognosis in critical care.

Comparação da acurácia de residentes, médicos seniores e decisores substitutos na previsão da mortalidade hospitalar de pacientes críticos / Comparison of the accuracy of residents, senior physicians and surrogate decision-makers for predicting hospital mortality of critically ill patients

RESUMO Objetivo: Comparar o desempenho preditivo de residentes, médicos seniores de unidades de terapia intensiva e decisores substitutos dos pacientes logo no início da internação na unidade de terapia intensiva e avaliar se diferentes apresentações de prognóstico (probabilidade de sobrevida versus probabilidade de óbito) influenciaram seus desempenhos. Métodos: Os decisores substitutos e os médicos responsáveis pelos pacientes críticos foram questionados durante as primeiras 48 horas de internação na unidade de terapia intensiva sobre a probabilidade do desfecho hospitalar do paciente. O enquadramento da pergunta (isto é, a probabilidade de sobrevida versus a probabilidade de óbito durante a internação) foi randomizado. Para avaliar o desempenho preditivo, comparou-se a área sob a curva ROC para desfecho hospitalar entre as categorias decisores substitutos e médicos. Também estratificaram-se os resultados de acordo com o enquadramento da pergunta randomizado. Resultados: Entrevistaram-se decisores substitutos e médicos sobre os desfechos hospitalares de 118 pacientes. O desempenho preditivo dos decisores substitutos foi significativamente inferior ao dos médicos (área sob a curva de 0,63 para decisores substitutos, 0,82 para residentes, 0,80 para residentes de medicina intensiva e 0,81 para médicos seniores de unidade de terapia intensiva). Não houve aumento no desempenho preditivo quanto à experiência dos médicos (ou seja, médicos seniores não previram desfechos melhor que médicos juniores). Os decisores substitutos pioraram seu desempenho de previsão quando perguntados sobre a probabilidade de óbito ao invés da probabilidade de sobrevida, mas não houve diferença entre os médicos. Conclusão: Observou-se desempenho preditivo diferente ao comparar decisores substitutos e médicos, sem qualquer efeito da experiência no prognóstico dos profissionais de saúde. O enquadramento da pergunta afetou o desempenho preditivo dos substitutos, mas não o dos médicos.

ABSTRACT Objective: To compare the predictive performance of residents, senior intensive care unit physicians and surrogates early during intensive care unit stays and to evaluate whether different presentations of prognostic data (probability of survival versus probability of death) influenced their performance. Methods: We questioned surrogates and physicians in charge of critically ill patients during the first 48 hours of intensive care unit admission on the patient's probability of hospital outcome. The question framing (i.e., probability of survival versus probability of death during hospitalization) was randomized. To evaluate the predictive performance, we compared the areas under the ROC curves (AUCs) for hospital outcome between surrogates and physicians' categories. We also stratified the results according to randomized question framing. Results: We interviewed surrogates and physicians on the hospital outcomes of 118 patients. The predictive performance of surrogate decisionmakers was significantly lower than that of physicians (AUC of 0.63 for surrogates, 0.82 for residents, 0.80 for intensive care unit fellows and 0.81 for intensive care unit senior physicians). There was no increase in predictive performance related to physicians' experience (i.e., senior physicians did not predict outcomes better than junior physicians). Surrogate decisionmakers worsened their prediction performance when they were asked about probability of death instead of probability of survival, but there was no difference for physicians. Conclusion: Different predictive performance was observed when comparing surrogate decision-makers and physicians, with no effect of experience on health care professionals' prediction. Question framing affected the predictive performance of surrogates but not of physicians.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

BACKGROUND: Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. METHODS: An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. RESULTS: Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. CONCLUSIONS: Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Patient-Centered Outcomes Following COVID-19: Frailty and Disability Transitions in Critical Care Survivors.

OBJECTIVES: As the pandemic advances, the interest in the long-lasting consequences of COVID-19 increases. However, a few studies have explored patient-centered outcomes in critical care survivors. We aimed to investigate frailty and disability transitions in COVID-19 patients admitted to ICUs. DESIGN: Prospective cohort study. SETTING: University hospital in Sao Paulo. PATIENTS: Survivors of COVID-19 ICU admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed frailty using the Clinical Frailty Scale (CFS). We also evaluated 15 basic, instrumental, and mobility activities. Baseline frailty and disability were defined by clinical conditions 2-4 weeks before COVID-19, and post-COVID-19 was characterized 90 days (day 90) after hospital discharge. We used alluvial flow diagrams to visualize transitions in frailty status, Venn diagrams to describe the overlap between frailty and disabilities in activities of daily living, and linear mixed models to explore the occurrence of new disabilities following critical care in COVID-19. We included 428 participants with a mean age of 64 years, 57% males, and a median Simplified Acute Physiology Score-3 score of 59. Overall, 14% were frail at baseline. We found that 124/394 participants (31%) were frail at day 90, 70% of whom were previously non-frail. The number of disabilities also increased (mean difference, 2.46; 95% CI, 2.06-2.86), mainly in participants who were non-frail before COVID-19. Higher pre-COVID-19 CFS scores were independently associated with new-onset disabilities. At day 90, 135 patients (34%) were either frail or disabled. CONCLUSIONS: Frailty and disability were more frequent 90 days after hospital discharge compared with baseline in COVID-19 patients admitted to the ICU. Our results show that most COVID-19 critical care survivors transition to poorer health status, highlighting the importance of long-term medical follow-up for this population.

Urinary sodium excretion is low prior to acute kidney injury in patients in the intensive care unit.

Background: The incidence of acute kidney injury (AKI) is high in intensive care units (ICUs), and a better understanding of AKI is needed. Early chronic kidney disease is associated with urinary concentration inability and AKI recovery with increased urinary solutes in humans. Whether the inability of the kidneys to concentrate urine and excrete solutes at appropriate levels could occur prior to the diagnosis of AKI is still uncertain, and the associated mechanisms have not been studied. Methods: In this single-center prospective observational study, high AKI risk in ICU patients was followed up for 7 days or until ICU discharge. They were grouped as "AKI" or "No AKI" according to their AKI status throughout admission. We collected daily urine samples to measure solute concentrations and osmolality. Data were analyzed 1 day before AKI, or from the first to the fifth day of admission in the "No AKI" group. We used logistic regression models to evaluate the influence of the variables on future AKI diagnosis. The expression of kidney transporters in urine was evaluated by Western blotting. Results: We identified 29 patients as "No AKI" and 23 patients as "AKI," the latter being mostly low severity AKI. Urinary sodium excretion was lower in "AKI" patients prior to AKI diagnosis, particularly in septic patients. The expression of Na+/H+ exchanger (NHE3), a urinary sodium transporter, was higher in "AKI" patients. Conclusions: Urinary sodium excretion is low before an AKI episode in ICU patients, and high expressions of proximal tubule sodium transporters might contribute to this.

Evaluation of eleven immunochromatographic assays for SARS-CoV-2 detection: investigating the dengue cross-reaction

ABSTRACT COVID-19 disease is spread worldwide and diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and a low-cost alternative especially in low and middle-income countries, which lack structure to perform certain diagnostic techniques. Here we evaluate the sensitivity and specificity of eleven different IC tests in 145 serum samples from confirmed cases of COVID-19 using RT-PCR and 100 negative serum samples from blood donors collected in February 2019. We also evaluated the cross-reactivity with dengue using 20 serum samples from patients with confirmed diagnosis for dengue collected in early 2019 through four different tests. We found high sensitivity (92%), specificity (100%) and an almost perfect agreement (Kappa 0.92) of IC assay, especially when we evaluated IgG and IgM combined after 10 days from the onset of symptoms with RT-PCR. However, we detected cross-reactivity between dengue and COVID-19 mainly with IgM antibodies (5 to 20% of cross-reaction) and demonstrated the need for better studies about diagnostic techniques for these diseases.