Development and validation of a nomogram for predicting 28-day mortality in patients with ischemic stroke.

BACKGROUND/AIM: We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations. MATERIALS AND METHODS: We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram's net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions. RESULTS: A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit. CONCLUSIONS: Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort.

Optimizing patient outcomes: a comprehensive evaluation of protocolized sedation in intensive care settings: a systematic review and meta-analysis.

INTRODUCTION: Amidst the routine utilization of protocolized sedation in ventilated ICU patients, existing management guidelines exhibit a lack of unanimous recommendations for its widespread adoption. This study endeavors to comprehensively assess the effectiveness and safety of protocolized sedation in critically ill ventilated patients. OBJECTIVE: The primary objective of this study was to systematically review and conduct a meta-analysis of clinical trials comparing protocolized sedation with standard management in critically ill ventilated patients. Key outcomes under scrutiny include ICU and hospital mortality, ventilation days, duration of ICU stay, and incidents of self-extubation. The evaluation incorporates the Risk of Bias 2 (RoB2) tool to assess the quality of included studies. Data analysis utilizes a random-effects model for relative risk (RR) and mean differences. Subgroup analysis categorizes sedation protocols into algorithmic or daily interruption, addressing potential heterogeneity. Additionally, a GRADE evaluation is performed to ascertain the overall certainty of the evidence. RESULTS: From an initial pool of 1504 records, 10 studies met the inclusion criteria. Protocolized sedation demonstrated a reduced RR for mortality (RR: 0.80, 95% CI 0.68-0.93, p < 0.01, I2 = 0%) and a decrease in ventilation days (mean difference: - 1.12, 95% CI - 2.11 to - 0.14, p = 0.03, I2 = 84%). Furthermore, there was a notable reduction in ICU stay (mean difference: - 2.24, 95% CI - 3.59 to - 0.89, p < 0.01, I2 = 81%). However, incidents of self-extubation did not exhibit a significant difference (RR: 1.20, 95% CI 0.49-2.94, p = 0.69, I2 = 35%). Subgroup analyses effectively eliminated heterogeneity (I2 = 0%), and the GRADE evaluation yielded moderate results for mortality, ventilation days, and ICU duration. CONCLUSION: Protocolized sedation, whether implemented algorithmically or through daily interruption, emerges as a safe and effective approach when compared to standard management in ventilated ICU patients. The findings from this study contribute valuable insights to inform evidence-based practices in sedation management for this critical patient population.

Association between high-flow nasal cannula use and mortality in patients with sepsis-induced acute lung injury: a retrospective propensity score-matched cohort study.

BACKGROUND: High-flow nasal cannula (HFNC) has emerged as a promising noninvasive method for delivering oxygen to critically ill patients, particularly those with sepsis and acute lung injury. However, uncertainties persist regarding its therapeutic benefits in this specific patient population. METHODS: This retrospective study utilized a propensity score-matched cohort from the Medical Information Mart in Intensive Care-IV (MIMIC-IV) database to explore the correlation between HFNC utilization and mortality in patients with sepsis-induced acute lung injury. The primary outcome was 28-day all-cause mortality. RESULTS: In the propensity score-matched cohort, the 28-day all-cause mortality rate was 18.63% (95 out of 510) in the HFNC use group, compared to 31.18% (159 out of 510) in the non-HFNC group. The use of HFNC was associated with a lower 28-day all-cause mortality rate (hazard ratio [HR] = 0.53; 95% confidence interval [CI] = 0.41-0.69; P < 0.001). HFNC use was also associated with lower ICU mortality (odds ratio [OR] = 0.52; 95% CI = 0.38-0.71; P < 0.001) and lower in-hospital mortality (OR = 0.51; 95% CI = 0.38-0.68; P < 0.001). Additionally, HFNC use was found to be associated with a statistically significant increase in both the ICU and overall hospitalization length. CONCLUSIONS: These findings indicate that HFNC may be beneficial for reducing mortality rates among sepsis-induced acute lung injury patients; however, it is also associated with longer hospital stays.

Value of serum iron and urine neutrophil gelatinase-associated lipocalin in predicting the mortality of critically ill patients with sepsis.

INTRODUCTION: We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis. METHODS: Serum or urine concentrations of iron metabolism-related parameters on intensive care unit admission were measured in a prospective cohort of 133 eligible patients with sepsis according to the Sepsis-3 criteria, and these values were compared between survivors and nonsurvivors, categorized according to their 60-day survival status. Cox regression analyses were performed to examine the association between iron parameters and 60-day mortality. Kaplan-Meier methods were used to illustrate the differences in survival between different iron parameters. RESULTS: Of the 133 patients included in the study, 61 (45.8%) had died by day 60. After adjusting for confounding variables, higher concentrations of serum iron (cut-off 9.5 µmol/mL) and higher concentrations of urine neutrophil gelatinase-associated lipocalin (uNGAL; cut-off 169.3 ng/mL) were associated with a significantly greater risk of death in the Cox regression analysis. These two biomarkers combined with Sequential Organ Failure Assessment (SOFA) scores increased the area under the receiver operating characteristic (AUROC) curve to 0.85. DISCUSSION: These findings suggest that higher concentrations of serum iron and uNGAL are each associated with higher 60-day mortality, and they add significant accuracy to this prediction in combination with SOFA. Abbreviations: uNGAL: urine neutrophil gelatinase-associated lipocalin; ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment; APACHE II: the Acute Physiology and Chronic Health Evaluation II; ELISA: enzyme-linked immunosorbent assay; HR: hazard ratio; CIs: confidence intervals; WBC: white blood cell; TBIL: total bilirubin.

Prediction of hospital mortality among critically ill patients in a single centre in Asia: comparison of artificial neural networks and logistic regression-based model.

INTRODUCTION: This study compared the performance of the artificial neural network (ANN) model with the Acute Physiologic and Chronic Health Evaluation (APACHE) II and IV models for predicting hospital mortality among critically ill patients in Hong Kong. METHODS: This retrospective analysis included all patients admitted to the intensive care unit of Pamela Youde Nethersole Eastern Hospital from January 2010 to December 2019. The ANN model was constructed using parameters identical to the APACHE IV model. Discrimination performance was assessed using area under the receiver operating characteristic curve (AUROC); calibration performance was evaluated using the Brier score and Hosmer-Lemeshow statistic. RESULTS: In total, 14 503 patients were included, with 10% in the validation set and 90% in the ANN model development set. The ANN model (AUROC=0.88, 95% confidence interval [CI]=0.86-0.90, Brier score=0.10; P in Hosmer-Lemeshow test=0.37) outperformed the APACHE II model (AUROC=0.85, 95% CI=0.80-0.85, Brier score=0.14; P<0.001 for both comparisons of AUROCs and Brier scores) but showed performance similar to the APACHE IV model (AUROC=0.87, 95% CI=0.85-0.89, Brier score=0.11; P=0.34 for comparison of AUROCs, and P=0.05 for comparison of Brier scores). The ANN model demonstrated better calibration than the APACHE II and APACHE IV models. CONCLUSION: Our ANN model outperformed the APACHE II model but was similar to the APACHE IV model in terms of predicting hospital mortality in Hong Kong. Artificial neural networks are valuable tools that can enhance real-time prognostic prediction.

Simvastatin in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2). RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control. CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. Objective: To determine whether vitamin C improves outcomes for patients with COVID-19. Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy. Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).

Temporal Clustering of Critical Illness Events on Medical Wards.

Importance: Recognizing and preventing patient deterioration is important for hospital safety. Objective: To investigate whether critical illness events (in-hospital death or intensive care unit [ICU] transfer) are associated with greater risk of subsequent critical illness events for other patients on the same medical ward. Design, Setting, and Participants: Retrospective cohort study in 5 hospitals in Toronto, Canada, including 118 529 hospitalizations. Patients were admitted to general internal medicine wards between April 1, 2010, and October 31, 2017. Data were analyzed between January 1, 2020, and April 10, 2023. Exposures: Critical illness events (in-hospital death or ICU transfer). Main Outcomes and Measures: The primary outcome was the composite of in-hospital death or ICU transfer. The association between critical illness events on the same ward across 6-hour intervals was studied using discrete-time survival analysis, adjusting for patient and situational factors. The association between critical illness events on different comparable wards in the same hospital was measured as a negative control. Results: The cohort included 118 529 hospitalizations (median age, 72 years [IQR, 56-83 years]; 50.7% male). Death or ICU transfer occurred in 8785 hospitalizations (7.4%). Patients were more likely to experience the primary outcome after exposure to 1 prior event (adjusted odds ratio [AOR], 1.39; 95% CI, 1.30-1.48) and more than 1 prior event (AOR, 1.49; 95% CI, 1.33-1.68) in the prior 6-hour interval compared with no exposure. The exposure was associated with increased odds of subsequent ICU transfer (1 event: AOR, 1.67; 95% CI, 1.54-1.81; >1 event: AOR, 2.05; 95% CI, 1.79-2.36) but not death alone (1 event: AOR, 1.08; 95% CI, 0.97-1.19; >1 event: AOR, 0.88; 95% CI, 0.71-1.09). There was no significant association between critical illness events on different wards within the same hospital. Conclusions and Relevance: Findings of this cohort study suggest that patients are more likely to be transferred to the ICU in the hours after another patient's critical illness event on the same ward. This phenomenon could have several explanations, including increased recognition of critical illness and preemptive ICU transfers, resource diversion to the first event, or fluctuations in ward or ICU capacity. Patient safety may be improved by better understanding the clustering of ICU transfers on medical wards.

Injectable Lipid Emulsion and Clinical Outcomes in Patients Exclusively Receiving Parenteral Nutrition in an ICU: A Retrospective Cohort Study Using a Japanese Medical Claims Database.

Guidelines for the nutritional management of critically ill patients recommend the use of injectable lipid emulsion (ILE) as part of parenteral nutrition (PN). The ILE's impact on outcomes remains unclear. Associations between prescribed ILE and in-hospital mortality, hospital readmission, and hospital length of stay (LOS) in critically ill patients in the intensive care unit (ICU) were investigated. Patients who were ≥18 years old in an ICU from January 2010 through June 2020, receiving mechanical ventilation, and fasting for >7 days, were selected from a Japanese medical claims database and divided, based on prescribed ILE during days from 4 to 7 of ICU admission, into 2 groups, no-lipid and with-lipid. Associations between the with-lipid group and in-hospital mortality, hospital readmission, and hospital LOS were evaluated relative to the no-lipid group. Regression analyses and the Cox proportional hazards model were used to calculate the odds ratios (OR) and regression coefficients, and hazard ratios (HR) were adjusted for patient characteristics and parenteral energy and amino acid doses. A total of 20,773 patients were evaluated. Adjusted OR and HR (95% confidence interval) for in-hospital mortality were 0.66 (0.62-0.71) and 0.68 (0.64-0.72), respectively, for the with-lipid group relative to the no-lipid group. No significant differences between the two groups were observed for hospital readmission or hospital LOS. The use of ILE for days 4 to 7 in PN prescribed for critically ill patients, who were in an ICU receiving mechanical ventilation and fasting for more than 7 days, was associated with a significant reduction in in-hospital mortality.

La suplementación parenteral con ácidos grasos omega-3 EPA/DHA mejora el pronóstico de recuperación en los pacientes críticos / Parenteral supplementation with EPA/DHA omega-3 fatty acids improves recovery prognosis in critically ill patients

Introducción: la decisión de suplementar la nutrición parenteral total (NPT) con emulsiones de los ácidos grasos (AG) omega-3 (Ω3) eicosapentaenoico (EPA) y docosahexaenoico (DHA) de origen marino se basa en los beneficios clínicos obtenidos en distintas situaciones médicas y quirúrgicas, entre los que destacan la reducción de la estancia hospitalaria, de los días de ventilación mecánica, de la incidencia de infecciones y de la mortalidad. Sin embargo, la evidencia en pacientes críticos aún es contradictoria. Objetivo: el objetivo de este ensayo clínico fue analizar el efecto de la suplementación con AG Ω3 EPA/DHA sobre los marcadores de pronóstico clínico: médicos, nutricionales y bioquímicos, en pacientes en estado crítico, en relación con el desenlace. Método: ensayo clínico, controlado, aleatorizado y unicéntrico en 64 pacientes adultos con condición crítica, de los cuales 47 pacientes se aleatorizaron para recibir NPT suplementada con AG Ω3 EPA/DHA a dosis de 0,1 g/kg/día (n = 23) o 0,2 g/kg/día (n = 24), comparados con un grupo de control histórico con NPT sin suplementación (n = 17). Se determinaron de manera basal y al final del soporte nutricional los marcadores de pronóstico clínico: médicos, nutricionales y bioquímicos. Resultados: los dos grupos con suplementación mostraron una reducción estadísticamente significativa de la mortalidad (p < 0,005); los marcadores de pronóstico clínico: SOFA, APACHE II, SAPS 3, NUTRIC, RTL y CRS, fueron consistentes en mostrar una mejoría significativa (p < 0,005) del pronóstico con las dosis de 0,1 y 0,2 g/kg/día de AG Ω3 EPA/DHA, respectivamente. Conclusión: la suplementación de la nutrición parenteral con ácidos grasos AG Ω3 EPA/DHA a dosis de 0,1 g y 0,2 g/kg/día mejora el pronóstico de la recuperación y la probabilidad de sobrevida en los pacientes críticos. (AU)

Introduction: the decision to supplement total parenteral nutrition (TPN) with emulsions of omega-3 (Ω3) eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids (FA) of marine origin is based on the clinical benefits obtained in different medical situations and surgical procedures, among which reductions in hospital stay, days of mechanical ventilation, incidence of infections and mortality stand out. However, the evidence in critically ill patients remains contradictory. Objective: the objective of this clinical trial was to analyze the effect of supplementation with EPA/DHA Ω3 FAs on clinical prognostic markers - medical, nutritional and biochemical - in critically ill patients, relating to outcome. Method: a clinical, controlled, randomized, single-center trial in 64 critically ill adult patients, of which 47 patients were randomized to receive TPN supplemented with EPA/DHA Ω3 FAs in doses of 0.1 g/kg/day (n = 23) and 0.2 g/kg/day (n = 24), compared with a historical control group with TPN without supplementation (n = 17). Clinical prognosis markers were determined at baseline and at the end of nutritional support (medical, nutritional and biochemical). Results: the two groups with supplementation showed a statistically significant reduction in mortality (p < 0.005); the clinical prognostic markers SOFA, APACHE II, SAPS 3, NUTRIC, RTL and CRS were consistent in showing a significant improvement (p < 0.005), of prognosis with doses of 0.1 and 0.2 g/kg/day of EPA/DHA Ω3 FAs, respectively. Conclusion: supplementation of parenteral nutrition with EPA/DHA Ω3 fatty acids at doses of 0.1 g and 0.2 g/kg/day improves recovery prognosis and the probability of survival in critically ill patients. (AU)

Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

Importance: The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. Objective: To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care. Data Sources: The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022. Study Selection: Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo. Data Extraction and Synthesis: Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework. Main Outcomes and Measures: The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms. Results: There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty. Conclusions and Relevance: Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.

Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain. Objective: To determine whether SDD reduces in-hospital mortality in critically ill adults. Design, Setting, and Participants: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021. Interventions: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care. Main Outcomes and Measures: The primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs. Results: Of 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, -1.7% [95% CI, -4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, -11.0%; 95% CI, -14.7% to -7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, -1.95%; 95% CI, -3.5% to -0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, -0.24%; 95% CI, -0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (-3.3% vs -1.59%; mean difference, -1.71% [1-sided 97.5% CI, -∞ to 4.31%] and 0.88% vs 0.55%; mean difference, -0.32% [1-sided 97.5% CI, -∞ to 5.47%]) in the first and second periods, respectively. Conclusions and Relevance: Among critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT02389036.

Homocysteine and the Mortality of Critically Ill Patients: A Meta-Analysis.

Prevalence of hyperhomocysteinemia (HHcy) is high in critically ill patients. However, the association between serum homocysteine level and outcomes of the critically ill patients remains unknown. We performed a meta-analysis of cohort studies to comprehensively evaluate the above association. Relevant cohort studies were identified by search of electronic databases including PubMed, Embase, Web of Science, Wanfang, and CNKI from the inception of the databases to February 5, 2022. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Overall, 16 cohorts with 1663 critically ill patients who were admitted to the intensive care unit (ICU) were involved in the meta-analysis. Pooled results showed that compared to non-survivors of the critical illnesses, survivors had significantly lower serum level of Hcy at ICU admission [mean difference (MD): -3.42 µmol/l, 95% confidence interval (CI): -5.89 to 0.94, p=0.007; I2=86%]. Subgroup analysis showed that the difference of Hcy between survivors and non-survivors was significant in Asian patients (MD: -8.17 µmol/l, p<0.001), but not in non-Asians (MD: 0.30 µmol/l, p=0.62; p for subgroup difference<0.001). Moreover, meta-analysis with seven cohorts, all including Chinese patients, showed that HHcy at ICU admission was independently associated with a higher risk of all-cause mortality in critically ill patients (odds ratio: 2.99, 95% CI: 2.26 to 3.97, p<0.001; I2=69%). A higher serum level of Hcy at ICU admission may be associated with an increased risk of all-cause mortality in critically ill patients, particularly in the Chinese population.

Predictors and outcome of time to presentation among critically ill paediatric patients at Emergency Department of Muhimbili National Hospital, Dar es Salaam, Tanzania.

BACKGROUND: Mortality among under-five children in Tanzania remains high. While early presentation for treatment increases likelihood of survival, delays to care are common and factors causing delay to presentation among critically ill children are unknown. In this study delay was defined as presentation to the emergency department of tertially hospital i.e. Muhimbili National Hospital, more than 48 h from the onset of the index illness. METHODOLOGY: This was a prospective cohort study of critically ill children aged 28 days to 14 years attending emergency department at Muhimbili National Hospital in Tanzania from September 2019 to January 2020. We documented demographics, time to ED presentation, ED interventions and 30-day outcome. The primary outcome was the association of delay with mortality and secondary outcomes were predictors of delay among critically ill paediatric patients. Logistic regression and relative risk were calculated to measure the strength of the predictor and the relationship between delay and mortality respectively. RESULTS: We enrolled 440 (59.1%) critically ill children, their median age was 12 [IQR = 9-60] months and 63.9% were males. The median time to Emergency Department arrival was 3 days [IQR = 1-5] and more than half (56.6%) of critically ill children presented to Emergency Department in > 48 h whereby being an infant, self-referral and belonging to poor family were independent predictors of delay. Infants and those referred from other facilities had 2.4(95% CI 1.4-4.0) and 1.8(95% CI 1.1-2.8) times increased odds of presenting late to the Emergency Department respectively. The overall 30-day in-hospital mortality was 26.5% in which those who presented late were 1.3 more likely to die than those who presented early (RR = 1.3, CI: 0.9-1.9). Majority died > 24 h of Emergency Department arrival (P-value = 0.021). CONCLUSION: The risk of in-hospital mortality among children who presented to the ED later than 48 h after onset of illness was 1.3 times higher than for children who presented earlier than 48 h. It could be anywhere from 10% lower to 90% higher than the point estimate. However, the effect size was statistically not significant since the confidence interval included the null value Qualitative and time-motion studies are needed to evaluate the care pathway of critically ill pediatric patients to identify preventable delays in care.

Extravascular lung water levels are associated with mortality: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of extravascular lung water (EVLW) measured by transpulmonary thermodilution (TPTD) in critically ill patients is debated. We performed a systematic review and meta-analysis of studies assessing the effects of TPTD-estimated EVLW on mortality in critically ill patients. METHODS: Cohort studies published in English from Embase, MEDLINE, and the Cochrane Database of Systematic Reviews from 1960 to 1 June 2021 were systematically searched. From eligible studies, the values of the odds ratio (OR) of EVLW as a risk factor for mortality, and the value of EVLW in survivors and non-survivors were extracted. Pooled OR were calculated from available studies. Mean differences and standard deviation of the EVLW between survivors and non-survivors were calculated. A random effects model was computed on the weighted mean differences across the two groups to estimate the pooled size effect. Subgroup analyses were performed to explore the possible sources of heterogeneity. RESULTS: Of the 18 studies included (1296 patients), OR could be extracted from 11 studies including 905 patients (464 survivors vs. 441 non-survivors), and 17 studies reported EVLW values of survivors and non-survivors, including 1246 patients (680 survivors vs. 566 non-survivors). The pooled OR of EVLW for mortality from eleven studies was 1.69 (95% confidence interval (CI) [1.22; 2.34], p < 0.0015). EVLW was significantly lower in survivors than non-survivors, with a mean difference of -4.97 mL/kg (95% CI [-6.54; -3.41], p < 0.001). The results regarding OR and mean differences were consistent in subgroup analyses. CONCLUSIONS: The value of EVLW measured by TPTD is associated with mortality in critically ill patients and is significantly higher in non-survivors than in survivors. This finding may also be interpreted as an indirect confirmation of the reliability of TPTD for estimating EVLW at the bedside. Nevertheless, our results should be considered cautiously due to the high risk of bias of many studies included in the meta-analysis and the low rating of certainty of evidence. Trial registration the study protocol was prospectively registered on PROSPERO: CRD42019126985.