Long-Term Mortality and Health-Related Quality of Life After Continuous Versus Intermittent Renal Replacement Therapy in ICU Survivors: A Secondary Analysis of the Quality of Life After ICU Study.

Purpose: We assessed long-term outcomes in intensive care unit (ICU) survivors with acute kidney injury (AKI) submitted to intermittent or continuous renal replacement therapy (RRT) for comparisons between groups. Methods: The multicenter prospective cohort study included 195 adult ICU survivors with an ICU stay >72 h in 10 ICUs that had at least one episode of AKI treated with intermittent RRT (IRRT) or continuous RRT (CRRT) during ICU stay. The main outcomes were mortality and health-related quality of life (HRQoL). Hospital readmissions and physical dependence were also assessed. Results: Regarding RRT, 83 (42.6%) patients received IRRT and 112 (57.4%) received CRRT. Despite the similarity regarding sociodemographic characteristics, pre-ICU state of health and type of admission between groups, the risk of death (23.5% vs 42.7%; P < .001), the prevalence of sepsis (60.7%) and acute respiratory distress syndrome (17%) were higher at ICU admission among CRRT patients. The severity of critical illness was higher among CRRT patients, regarding the need for mechanical ventilation (75.0% vs 50.6%, P = .002) and vasopressors (91.1% vs 63.9%, P < .001). One year after ICU discharge, 67 of 195 ICU survivors died (34.4%) and, after adjustment for confounders, there were no significant differences in mortality when comparing IRRT and CRTT patients (34.9% vs 33.9%; P = .590), on HRQoL in both physical (41.9% vs 42.2%; P = .926) and mental dimensions (57.6% vs 56.6%; P = .340), and on the number of hospital readmissions and physical dependence. Conclusions: Our study suggests that among ICU survivors RRT modality (IRRT vs CRRT) in the ICU does not impact long-term outcomes after ICU discharge.

Lower quality of life in obese ICU survivors: a multicenter cohort study.

PURPOSE: To compare health-related quality of life (HRQoL) and functional status between obese, underweight, normal-weight, and overweight patients after three months post-intensive care unit (ICU) discharge. METHODS: Multicenter cohort study (10 Brazilian ICUs). 1600 ICU survivors (≥ 72 h in the ICU) were included.The main outcomes were HRQoL and functional status assessed three months after the ICU discharge. The secondary outcomes were mortality, hospital readmission, and ICU readmission during the same period. RESULTS: Obese patients (median 50.1; IQR 39.6-59.6) had lower HRQoL in the mental component than normal-weight patients (median 53; IQR 45.6-60.1) (p = 0.033). No differences were found between BMI categories regarding the physical component of HRQoL and the Barthel Index (p = 0.355 and 0.295, respectively). Regarding readmissions, 65.1 and 25.1% of patients were readmitted to the hospital and ICU, but there was no difference between the groups (p = 0.870 and 0.220, respectively). Obese patients died less frequently (11.8%) than underweight (30.9%) and normal-weight (19.3%) patients (p < 0.001). CONCLUSION: After three months of post-ICU discharge, obese patients had lower HRQoL in the mental component than normal-weight patients. However, obese patients died less than underweight and normal-weight patients.

Reply to the letter "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients".

This is a reply to the letter titled "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients" by Eva Rully Kurniawati et al. In response to the concerns raised about our paper published in BMC Cardiovascular Disorders, titled "Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study," we have addressed the confounding bias on the population included and the use of VA-ECMO and Impella CP. Furthermore, we have provided new data on the correlation of oxygen supply and lactate levels at admission of cardiogenic shock.

Convalescent plasma for COVID-19 in hospitalised patients: an open-label, randomised clinical trial.

BACKGROUND: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. METHODS: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. RESULTS: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48-68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8-12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference -3.7%, 95% CI -18.8-11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. CONCLUSIONS: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone.

Mechanism of a Flexible ICU Visiting Policy for Anxiety Symptoms Among Family Members in Brazil: A Path Mediation Analysis in a Cluster-Randomized Clinical Trial.

OBJECTIVES: To investigate whether the effect of a flexible ICU visiting policy that includes flexible visitation plus visitor education on anxiety symptoms of family members is mediated by satisfaction and involvement in patient care. DESIGN: We embedded a multivariable path mediation analysis within a cluster-randomized crossover trial as a secondary analysis of The ICU Visits Study (ClinicalTrials.gov number: NCT02932358). SETTING: Thirty-six medical-surgical ICUs in Brazil. PATIENTS: Closest relatives of adult ICU patients. INTERVENTIONS: Flexible visitation (12 hr/d) supported by family education or usual restricted visitation (median, 1.5 hr/d). MEASUREMENTS AND MAIN RESULTS: Overall, 863 family members were assessed (mean age, 44.7 yr; women, 70.1%). Compared with the restricted visitation (n = 436), flexible visitation (n = 427) resulted in better mean anxiety scores (6.1 vs 7.8; mean difference, -1.78 [95% CI, -2.31 to -1.22]), as well as higher standardized scores of satisfaction (67% [95% CI, 55-79]) and involvement in patient care (77% [95% CI, 64-89]). The mediated effect of flexible visitation on mean anxiety scores through each incremental sd of satisfaction and involvement in patient care were -0.47 (95% CI, -0.68 to -0.24) and 0.29 (95% CI, 0.04-0.54), respectively. Upon exploratory analyses, emotional support, helping the ICU staff to understand patient needs, helping the patient to interpret ICU staff instructions, and patient reorientation were the domains of involvement in patient care associated with increased anxiety. CONCLUSIONS: A flexible ICU visiting policy reduces anxiety symptoms among family members and appears to work by increasing satisfaction. However, increased participation in some activities of patient care as a result of flexible visitation was associated with higher severity of anxiety symptoms.

Brazilian Translation, Cross-Cultural Adaptation, Validity, and Reliability of the EMpowerment of PArents in THe Intensive Care 30 (EMPATHIC-30) Questionnaire to Measure Parental Satisfaction in PICUs.

OBJECTIVES: To conduct the Brazilian translation, cross-cultural adaptation, validation, and reliability testing of the EMpowerment of PArents in THe Intensive Care (EMPATHIC-30). DESIGN: Prospective study. SETTING: PICU of a tertiary-care teaching hospital. PATIENTS: Parents (n = 141) completed the translated EMPATHIC-30 questionnaire 72 hours after their child's PICU discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The translation and cultural adaptation were performed in accordance with the principles of good practice for the translation and cultural adaptation process for patient-reported outcomes measures. Sentences were adapted according to the Brazilian syntax. Total content validity coefficient was above the established average (> 0.8). Reliability was evaluated with the coefficients McDonald omega and Cronbach alpha. The lowest Cronbach alpha found was 0.47 (CI 95%, 0.35-0.59) in the organization domain, where the lowest response rate was also concentrated. The values of the other domains were as follows: 0.64 (95% CI, 0.55-0.73) for information, 0.77 (95% CI, 0.71-0.83) for care and treatment, 0.72 (95% CI, 0.66-0.78) for parent participation, and 0.72 (95% CI, 0.65-0.79) for professional attitudes. The total internal consistency independent of the domain was 0.90 (CI 95%, 0.88-0.92). With regard to McDonald Omega, values were identified: 0.68 (95% CI, 0.49-0.88) for information, 0.73 (95% CI, 0.61-0.85) for care and treatment, 0.85 (95% CI, 0.47-0.80) for parent participation, 0.85 (95% CI, 0.76-0.93), and 0.72 (95% CI, 0.58-0.86) for professional attitudes. CONCLUSIONS: EMPATHIC-30 has been translated and culturally adapted for the Brazilian population. Validation demonstrated an above-average total content validity coefficient, confirming the instrument content validity. A sufficient reliability was observed in both analyzed coefficients. The results support the use of the Brazilian version of EMPATHIC-30 for the evaluation of parents' satisfaction of children admitted to the PICU.

Early and Late Mortality Following Discharge From the ICU: A Multicenter Prospective Cohort Study.

OBJECTIVES: To identify the frequency, causes, and risk factors of early and late mortality among general adult patients discharged from ICUs. DESIGN: Multicenter, prospective cohort study. SETTING: ICUs of 10 tertiary hospitals in Brazil. PATIENTS: One-thousand five-hundred fifty-four adult ICU survivors with an ICU stay greater than 72 hours for medical and emergency surgical admissions or greater than 120 hours for elective surgical admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcomes were early (30 d) and late (31 to 365 d) mortality. Causes of death were extracted from death certificates and medical records. Twelve-month cumulative mortality was 28.2% (439 deaths). The frequency of early mortality was 7.9% (123 deaths), and the frequency of late mortality was 22.3% (316 deaths). Infections were the leading cause of death in both early (47.2%) and late (36.4%) periods. Multivariable analysis identified age greater than or equal to 65 years (hazard ratio, 1.65; p = 0.01), pre-ICU high comorbidity (hazard ratio, 1.59; p = 0.02), pre-ICU physical dependence (hazard ratio, 2.29; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.008; p = 0.03), ICU-acquired infections (hazard ratio, 2.25; p < 0.001), and ICU readmission (hazard ratio, 3.76; p < 0.001) as risk factors for early mortality. Age greater than or equal to 65 years (hazard ratio, 1.30; p = 0.03), pre-ICU high comorbidity (hazard ratio, 2.28; p < 0.001), pre-ICU physical dependence (hazard ratio, 2.00; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.010; p < 0.001), and ICU readmission (hazard ratios, 4.10, 4.17, and 1.82 for death between 31 and 60 days, 61 and 90 days, and greater than 90 days after ICU discharge, respectively; p < 0.001 for all comparisons) were associated with late mortality. CONCLUSIONS: Infections are the main cause of death after ICU discharge. Older age, pre-ICU comorbidities, pre-ICU physical dependence, severity of illness at ICU admission, and ICU readmission are associated with increased risk of early and late mortality, while ICU-acquired infections are associated with increased risk of early mortality.

Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study.

BACKGROUND: To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP®. METHODS: Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality. RESULTS: VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67-0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality. CONCLUSIONS: Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.

Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care Unit: The ICU Visits Randomized Clinical Trial.

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain. Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation. Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium. Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.

Performance of the SHARPEN Score and the Charlson Comorbidity Index for In-Hospital and Post-Discharge Mortality Prediction in Infective Endocarditis. / Desempenho do Escore SHARPEN e do Índice de Comorbidade de Charlson para Predição de Mortalidade durante a Internação Hospitalar e após a Alta na Endocardite Infecciosa.

BACKGROUND: Central Illustration : Performance of the SHARPEN Score and the Charlson Comorbidity Index for In-Hospital and Post-Discharge Mortality Prediction in Infective Endocarditis. BACKGROUND: SHARPEN was the first dedicated score for in-hospital mortality prediction in infective endocarditis (IE) regardless of cardiac surgery. OBJECTIVES: To analyze the ability of the SHARPEN score to predict in-hospital and post-discharge mortality and compare it with that of the Charlson comorbidity index (CCI). METHODS: Retrospective cohort study including definite IE (Duke modified criteria) admissions from 2000 to 2016. The area under the ROC curve (AUC-ROC) was calculated to assess predictive ability. Kaplan-Meier curves and Cox regression was performed. P-value < 0.05 was considered statistically significant. RESULTS: We studied 179 hospital admissions. In-hospital mortality was 22.3%; 68 (38.0%) had cardiac surgery. Median (interquartile range, IQR) SHARPEN and CCI scores were 9(7-11) and 3(2-6), respectively. SHARPEN had better in-hospital mortality prediction than CCI in non-operated patients (AUC-ROC 0.77 vs. 0.62, p = 0.003); there was no difference in overall (p = 0.26) and in operated patients (p = 0.41). SHARPEN > 10 at admission was associated with decreased in-hospital survival in the overall (HR 3.87; p < 0.001), in non-operated (HR 3.46; p = 0.006) and operated (HR 6.86; p < 0.001) patients. CCI > 3 at admission was associated with worse in-hospital survival in the overall (HR 3.0; p = 0.002), and in operated patients (HR 5.57; p = 0.005), but not in non-operated patients (HR 2.13; p = 0.119). Post-discharge survival was worse in patients with SHARPEN > 10 (HR 3.11; p < 0.001) and CCI > 3 (HR 2.63; p < 0.001) at admission; however, there was no difference in predictive ability between these groups. CONCLUSION: SHARPEN was superior to CCI in predicting in-hospital mortality in non-operated patients. There was no difference between the scores regarding post-discharge mortality.

Long-term effects of flexible visitation in the intensive care unit on family members' mental health: 12-month results from a randomized clinical trial.

PURPOSE: The aim of this study was to assess the effects of flexible intensive care unit (ICU) visitation on the 1-year prevalence of post-traumatic stress, anxiety and depression symptoms among family members of critically ill patients. METHODS: This is a long-term outcome analysis of a cluster-crossover randomized clinical trial that evaluated a flexible visitation model in the ICU (12 h/day) compared to a restrictive visitation model (median 1.5 h/day) in 36 Brazilian ICUs. In this analysis, family members were assessed 12 months after patient discharge from the ICU for the following outcomes: post-traumatic stress symptoms measured by the Impact Event Scale-6 and anxiety and depression symptoms measured by the Hospital Anxiety and Depression Scale. RESULTS: A total of 519 family members were analyzed (288 in the flexible visitation group and 231 in the restrictive visitation group). Three-hundred sixty-nine (71.1%) were women, and the mean age was 46.6 years. Compared to family members in the restrictive visitation group, family members in the flexible visitation group had a significantly lower prevalence of post-traumatic stress symptoms (21% vs. 30.5%; adjusted prevalence ratio [aPR], 0.91; 95% confidence interval [CI] 0.85-0.98; p = 0.01). The prevalence of anxiety (28.9% vs. 33.2%; aPR 0.93; 95% CI 0.72-1.21; p = 0.59) and depression symptoms (19.2% vs. 25%; aPR, 0.78; 95% CI 0.60-1.02; p = 0.07) did not differ significantly between the groups. CONCLUSION: Flexible ICU visitation, compared to the restrictive visitation, was associated with a significant reduction in the 1-year prevalence of post-traumatic stress symptoms in family members.

Long term cognitive dysfunction among critical care survivors: associated factors and quality of life-a multicenter cohort study.

OBJECTIVES: To identify the prevalence and associated factors of cognitive dysfunction, 1 year after ICU discharge, among adult patients, and it´s relation with quality of life. METHODS: Multicenter, prospective cohort study including ICUs of 10 tertiary hospitals in Brazil, between May 2014 and December 2018. The patients included were 452 adult ICU survivors (median age 60; 47.6% women) with an ICU stay greater than 72 h. RESULTS: At 12 months after ICU discharge, a Montreal Cognitive Assessment (tMOCA) telephone score of less than 12 was defined as cognitive dysfunction. At 12 months, of the 452 ICU survivors who completed the cognitive evaluation 216 (47.8%) had cognitive dysfunction. In multivariable analyses, the factors associated with long-term (1-year) cognitive dysfunction were older age (Prevalence Ratio-PR = 1.44, P < 0.001), absence of higher education (PR = 2.81, P = 0.005), higher comorbidities on admission (PR = 1.089; P = 0.004) and delirium (PR = 1.13, P < 0.001). Health-related Quality of life (HRQoL), assessed by the mental and physical dimensions of the SF-12v2, was significantly better in patients without cognitive dysfunction (Mental SF-12v2 Mean difference = 2.54; CI 95%, - 4.80/- 0.28; p = 0.028 and Physical SF-12v2 Mean difference = - 2.85; CI 95%, - 5.20/- 0.50; P = 0.018). CONCLUSIONS: Delirium was found to be the main modifiable predictor of long-term cognitive dysfunction in ICU survivors. Higher education consistently reduced the probability of having long-term cognitive dysfunction. Cognitive dysfunction significantly influenced patients' quality of life, leading us to emphasize the importance of cognitive reserve for long-term prognosis after ICU discharge.

Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5-11 years of age in Brazil: A prospective test-negative design study.

OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).

Does an educational website improve psychological outcomes and satisfaction among family members of intensive care unit patients?

OBJECTIVE: To evaluate the impact of an educational website on satisfaction and symptoms of anxiety and depression among family members of critically ill adult patients. METHODS: We embedded an analysis of website access in a cohort study conducted in intensive care units with flexible visiting hours in Brazil. Family members were guided to access an educational website designed to help them understand the processes and emotions associated with an intensive care unit stay. Subjects were evaluated for baseline data within the first 48 hours following enrollment and outcome assessment at up to 7 days after patient discharge from the intensive care unit, death, or until the 30th day of the study. The main outcomes were satisfaction using the Critical Care Family Needs Inventory and the presence of anxiety and depression symptoms using the Hospital Anxiety and Depression Scale. RESULTS: A total of 532 family members were evaluated during the study period. Of these, 61 (11.5%) accessed the website. After adjustments, family members who accessed the website had significantly better mean Critical Care Family Needs Inventory scores (152.8 versus 145.2, p = 0.01) and a lower prevalence of probable clinical anxiety (prevalence ratio 0.35; 95%CI 0.14 - 0.89) than family members who did not access the website. There were no differences regarding symptoms of depression. CONCLUSION: Access to an educational website was associated with higher family satisfaction with care and a lower prevalence of clinical anxiety.

Impact of vertical positioning on lung aeration among mechanically ventilated intensive care unit patients: a randomized crossover clinical trial.

OBJECTIVE: To assess the impact of different vertical positions on lung aeration in patients receiving invasive mechanical ventilation. METHODS: An open-label randomized crossover clinical trial was conducted between January and July 2020. Adults receiving invasive mechanical ventilation for > 24 hours and < 7 days with hemodynamic, respiratory and neurological stability were randomly assigned at a 1:1 ratio to the sitting position followed by passive orthostasis condition or the passive orthostasis followed by the sitting position condition. The primary outcome was lung aeration assessed using the lung ultrasound score (score ranges from 0 [better] to 36 [worse]). RESULTS: A total of 186 subjects were screened; of these subjects, 19 were enrolled (57.8% male; mean age, 73.2 years). All participants were assigned to receive at least one verticalization protocol. Passive orthostasis resulted in mean lung ultrasound scores that did not differ significantly from the sitting position (11.0 versus 13.7; mean difference, -2.7; [95%CI -6.1 to 0.71; p = 0.11). Adverse events occurred in three subjects in the passive orthostasis group and in one in the sitting position group (p = 0.99). CONCLUSION: This analysis did not find significant differences in lung aeration between the sitting and passive orthostasis groups. A randomized crossover clinical trial assessing the impact of vertical positioning on lung aeration in patients receiving invasive mechanical ventilation is feasible. Unfortunately, the study was interrupted due to the need to treat COVID-19 patients.ClinicalTrials.gov registry: NCT04176445.

BNT162b2 mRNA COVID-19 against symptomatic Omicron infection following a mass vaccination campaign in southern Brazil: A prospective test-negative design study.

BACKGROUND: Evidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant. METHODS: This prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19. RESULTS: A total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %-64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60-139 days). Effectiveness waned from 77.7 % at 7-29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days. CONCLUSION: In a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307).

Evidence-Based Checklist to Delay Cardiac Arrest in Brain-Dead Potential Organ Donors: The DONORS Cluster Randomized Clinical Trial.

Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear. Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU). Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020. Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care. Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group. Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006). Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist. Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.

Return to work after discharge from the intensive care unit: a Brazilian multicenter cohort. / Retorno ao trabalho após a alta da unidade de terapia intensiva: uma coorte multicêntrica brasileira.

OBJECTIVE: To describe the rate and factors related to nonreturn to work in the third month after discharge from the intensive care unit and the impact of unemployment, loss of income and health care expenses for survivors. METHODS: This was a prospective multicenter cohort study that included survivors of severe acute illness who were hospitalized between 2015 and 2018, previously employed, and who stayed more than 72 hours in the intensive care unit. Outcomes were assessed by telephone interview in the third month after discharge. RESULTS: Of the 316 patients included in the study who had previously worked, 193 (61.1%) did not return to work within 3 months after discharge from the intensive care unit. The following factors were associated with nonreturn to work: low educational level (prevalence ratio 1.39; 95%CI 1.10 - 1.74; p = 0.006), previous employment relationship (prevalence ratio 1.32; 95%CI 1 10 - 1.58; p = 0.003), need for mechanical ventilation (prevalence ratio 1.20; 95%CI 1.01 - 1.42; p = 0.04) and physical dependence in the third month after discharge (prevalence ratio 1.27; 95%CI 1.08 - 1.48; p = 0.003). Survivors who were unable to return to work more often had reduced family income (49.7% versus 33.3%; p = 0.008) and increased health expenditures (66.9% versus 48.3%; p = 0.002). compared to those who returned to work in the third month after discharge from the intensive care unit. CONCLUSION: Intensive care unit survivors often do not return to work until the third month after discharge from the intensive care unit. Low educational level, formal job, need for ventilatory support and physical dependence in the third month after discharge were related to nonreturn to work. Failure to return to work was also associated with reduced family income and increased health care costs after discharge.

OBJETIVO: Descrever a taxa e os fatores relacionados ao não retorno ao trabalho no terceiro mês pós-alta da unidade de terapia intensiva, além dos impactos do desemprego, da perda de renda e dos gastos com saúde para os sobreviventes. MÉTODOS: Estudo de coorte prospectivo multicêntrico, que incluiu sobreviventes da doença aguda grave, hospitalizados entre 2015 e 2018, previamente empregados, que permaneceram mais de 72 horas internados na unidade de terapia intensiva. Os desfechos foram avaliados por entrevista telefônica no terceiro mês após a alta. RESULTADOS: Dos 316 pacientes incluídos no estudo que trabalhavam previamente, 193 (61,1%) não retornaram ao trabalho nos 3 meses após a alta da unidade de terapia intensiva. Foram associados ao não retorno ao trabalho: baixo nível educacional (razão de prevalência de 1,39; IC95% 1,10 - 1,74; p = 0,006), vínculo empregatício prévio (razão de prevalência de 1,32; IC95% 1,10 - 1,58; p = 0,003), necessidade de ventilação mecânica (razão de prevalência de 1,20; IC95% 1,01 - 1,42; p = 0,04) e dependência física no terceiro mês pós-alta (razão de prevalência de 1,27; IC95% 1,08 - 1,48; p = 0,003). Os sobreviventes incapazes de retornar ao trabalho mais frequentemente apresentaram redução da renda familiar (49,7% versus 33,3%; p = 0,008) e aumento dos gastos em saúde (66,9% versus 48,3%; p = 0,002) quando comparados àqueles que retornaram ao trabalho no terceiro mês após a alta da unidade de terapia intensiva. CONCLUSÃO: Frequentemente, os sobreviventes de unidade de terapia intensiva não retornam ao trabalho até o terceiro mês pós-alta da unidade de terapia intensiva. Baixo nível educacional, trabalho formal, necessidade de suporte ventilatório e dependência física no terceiro mês pós-alta relacionaram-se ao não retorno ao trabalho. O não retorno ao trabalho também se relacionou com redução na renda familiar e aumento dos custos com saúde após a alta da unidade de terapia intensiva.

BNT162b2 against COVID-19 in Brazil using a test-negative design: Study protocol and statistical analysis plan.

INTRODUCTION: Real-world data on COVID-19 vaccine effectiveness are needed to validate evidence from randomized clinical trials. Accordingly, this study aims to evaluate, in a real-world setting in Brazil, the effectiveness of Pfizer-BioNTech BNT162b2 against symptomatic COVID-19 and COVID-19-related complications across diverse populations. MATERIALS AND METHODS: A test-negative case-control study with follow-up of cases is currently being conducted in Toledo, a city in southern Brazil, following a mass COVID-19 vaccination campaign with BNT162b2. The study is being conducted among patients aged 12 years or older seeking care in the public health system with acute respiratory symptoms and tested for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). Cases are RT-PCR positive and controls RT-PCR negative. Test-positive cases are prospectively followed through structured telephone interviews performed at 15 days post-enrollment, and at 1, 3, 6, 9 and 12 months. Baseline demographic, clinical, and vaccination data are being collected by means of structured interviews and medical registry records reviews at the time of enrollment. All RT-PCR-positive samples are screened for mutations to identify SARS-CoV-2 variants. ETHICS AND DISSEMINATION: The study protocol has been approved by the research ethics committee of all participant sites. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRAIL REGISTRATION: Clinicatrials.gov: NCT05052307.

IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units. / IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva.

OBJECTIVE: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. METHODS: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. RESULTS: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. CONCLUSION: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

OBJETIVO: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. MÉTODOS: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. RESULTADOS: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. CONCLUSÃO: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.