Evaluating the Sum of Eye and Motor Components of the Glasgow Coma Score As a Predictor of Extubation Failure in Patients With Acute Brain Injury.

OBJECTIVES: To evaluate the association between the pre-extubation sum of eye and motor components of the Glasgow Coma Score (GCS-EM) and odds of extubation failure in patients with acute brain injury being liberated from mechanical ventilation. DESIGN: Secondary analysis of a prospective, multicenter observational study (ClinicalTrials.gov identifier NCT03400904). SETTING: Sixty-three hospital sites worldwide, with patient recruitment from January 2018 to November 2020. PATIENTS: One thousand one hundred fifty-two critically ill patients with acute brain injury, with a median age of 54 years, of whom 783 (68.0%) were male, 559 (48.5%) had traumatic brain injury, and 905 (78.6%) had a GCS-EM greater than 8 before extubation (scores range from 2 to 10). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: GCS-EM was computed in intubated patients on the day of extubation. The main outcome was extubation failure, defined as unplanned reintubation within 5 days of extubation. Analyses used multilevel logistic regression with adjustment for patient characteristics and a random intercept for hospital site. In the primary analysis, GCS-EM was not associated with extubation failure (odds ratio, 1.07 per additional point; 95% CI, 0.87-1.31). Findings were consistent in sensitivity analyses that: 1) used different adjustment covariates, 2) included a verbal estimate to derive an overall GCS, 3) accounted for missing data, 4) considered a 2-day time interval to define extubation failure, 5) accounted for competing risks, and 6) used a propensity score-based model. There was no association between GCS-EM and extubation outcome in subgroups defined by brain injury diagnosis or age. CONCLUSIONS: In this large, contemporary, multicenter cohort of patients with acute brain injury, we found no association between the GCS-EM and odds of extubation failure. However, few patients had a pre-extubation GCS-EM less than or equal to 8, and the possibility of a true prognostic association in patients with low scores is not excluded.

New antipsychotic prescription and recurrent infections among adult sepsis survivors: A population-based cohort study.

PURPOSE: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D2 affinity. METHODS: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D2 affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D2 affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: Overall, 1879 patients filled a prescription for a high-D2, and 1446 patients filled a prescription for a low-D2 affinity antipsychotic. Patients who filled a prescription for a high-D2 affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D2 affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35). CONCLUSIONS: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D2 affinity antipsychotics (compared with low-D2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.

Accounting for Competing Events When Evaluating Long-Term Outcomes in Survivors of Critical Illness.

The clinical trajectory of survivors of critical illness after hospital discharge can be complex and highly unpredictable. Assessing long-term outcomes after critical illness can be challenging because of possible competing events, such as all-cause death during follow-up (which precludes the occurrence of an event of particular interest). In this perspective, we explore challenges and methodological implications of competing events during the assessment of long-term outcomes in survivors of critical illness. In the absence of competing events, researchers evaluating long-term outcomes commonly use the Kaplan-Meier method and the Cox proportional hazards model to analyze time-to-event (survival) data. However, traditional analytical and modeling techniques can yield biased estimates in the presence of competing events. We present different estimands of interest and the use of different analytical approaches, including changes to the outcome of interest, Fine and Gray regression models, cause-specific Cox proportional hazards models, and generalized methods (such as inverse probability weighting). Finally, we provide code and a simulated dataset to exemplify the application of the different analytical strategies in addition to overall reporting recommendations.

IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial.

OBJECTIVES: The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis. DESIGN: Bayesian reanalysis of a randomized placebo-controlled trial. SETTING: Thirty-five ICUs. PATIENTS: Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission. INTERVENTIONS: Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04-1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00-1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97-1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98-1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94-1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92-1.19; probability of harm, 76%) priors. CONCLUSIONS: The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.

Risk Factors for Major Cardiovascular Events in Adult Sepsis Survivors: A Population-Based Cohort Study.

OBJECTIVES: To describe risk factors for major cardiovascular events in adults following hospital discharge after sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2017). PATIENTS: Adult patients (age 18 yr or older) who survived a first sepsis hospitalization without preexisting cardiovascular disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5 years following hospital discharge. We used cause-specific Cox proportional hazards models that accounted for the competing risk of noncardiovascular death to describe factors associated with major cardiovascular events. We identified 268,259 adult patients without cardiovascular disease (median age, 72 yr), of whom 10.4% experienced a major cardiovascular event during a median follow-up of 3 years. After multivariable adjustment, age (hazard ratio [HR], 1.53 for every 10 yr; 95% CI, 1.51-1.54), male sex (HR, 1.23; 95% CI, 1.20-1.26), diabetes mellitus (HR, 1.24; 95% CI, 1.21-1.27), hypertension (HR, 1.34; 95% CI, 1.30-1.38), prevalent atrial fibrillation (HR, 1.46; 95% CI, 1.40-1.52), and chronic kidney disease (HR, 1.11; 95% CI, 1.06-1.16) were associated with major cardiovascular events during long-term follow-up. Sepsis characteristics such as site of infection (pneumonia vs other: HR, 1.09; 95% CI, 1.05-1.12), septic shock (HR, 1.08; 95% CI, 1.05-1.11), and renal replacement therapy (HR, 1.51; 95% CI, 1.38-1.64) were also associated with subsequent cardiovascular events. In an analysis restricting to patients with troponin values measured during the hospitalization (26,400 patients), an elevated troponin was also associated with subsequent cardiovascular events (HR, 1.23; 95% CI, 1.13-1.33). CONCLUSIONS: Classic cardiovascular risk factors, comorbid conditions, and characteristics of the sepsis episode were associated with a higher hazard of major cardiovascular events in adult sepsis survivors. These findings may inform enrichment strategies for future studies.

Prevalent diabetes and long-term cardiovascular outcomes in adult sepsis survivors: a population-based cohort study.

BACKGROUND: Sepsis survivors are at elevated risk for cardiovascular disease during long-term follow-up. Whether diabetes influences cardiovascular risk after sepsis survival remains unknown. We sought to describe the association of diabetes with long-term cardiovascular outcomes in adult sepsis survivors. METHODS: Population-based cohort study in the province of Ontario, Canada (2008-2017). Adult survivors of a first sepsis-associated hospitalization, without pre-existing cardiovascular disease, were included. Main exposure was pre-existing diabetes (any type). The primary outcome was the composite of myocardial infarction, stroke, and cardiovascular death. Patients were followed up to 5 years from discharge date until outcome occurrence or end of study period (March 2018). We used propensity score matching (i.e., 1:1 to patients with sepsis but no pre-existing diabetes) to adjust for measured confounding at baseline. Cause-specific Cox proportional hazards models with robust standard errors were used to estimate hazard ratios (HR) alongside 95% confidence intervals (CI). A main secondary analysis evaluated the modification of the association between sepsis and cardiovascular disease by pre-existing diabetes. RESULTS: 78,638 patients with pre-existing diabetes who had a sepsis-associated hospitalization were matched to patients hospitalized for sepsis but without diabetes. Mean age of patients was 71 years, and 55% were female. Median duration from diabetes diagnosis was 9.8 years; mean HbA1c was 7.1%. Adult sepsis survivors with pre-existing diabetes experienced a higher hazard of major cardiovascular disease (HR 1.25; 95% CI 1.22-1.29)-including myocardial infarction (HR 1.40; 95% CI 1.34-1.47) and stroke (HR 1.24; 95% CI 1.18-1.29)-during long-term follow-up compared to sepsis survivors without diabetes. Pre-existing diabetes modified the association between sepsis and cardiovascular disease (risk difference: 2.3%; 95% CI 2.0-2.6 and risk difference: 1.8%; 95% CI 1.6-2.0 for the effect of sepsis-compared to no sepsis-among patients with and without diabetes, respectively). CONCLUSIONS: Sepsis survivors with pre-existing diabetes experience a higher long-term hazard of major cardiovascular events when compared to sepsis survivors without diabetes. Compared to patients without sepsis, the absolute risk increase of cardiovascular events after sepsis is higher in patients with diabetes (i.e., diabetes intensified the higher cardiovascular risk induced by sepsis).

Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts.

BACKGROUND: The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation. METHODS: This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008-2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003-2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation. RESULTS: We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8). CONCLUSION: Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Helmet noninvasive ventilation compared to facemask noninvasive ventilation and high-flow nasal cannula in acute respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Although small randomised controlled trials (RCTs) and observational studies have examined helmet noninvasive ventilation (NIV), uncertainty remains regarding its role. We conducted a systematic review and meta-analysis to examine the effect of helmet NIV compared to facemask NIV or high-flow nasal cannula (HFNC) in acute respiratory failure. METHODS: We searched multiple databases to identify RCTs and observational studies reporting on at least one of mortality, intubation, intensive care unit (ICU) length of stay, NIV duration, complications or comfort with NIV therapy. We assessed study risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the Ottawa-Newcastle Scale for observational studies, and rated certainty of pooled evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) framework. RESULTS: We separately pooled data from 16 RCTs (n=949) and eight observational studies (n=396). Compared to facemask NIV, based on low certainty of evidence, helmet NIV may reduce mortality (relative risk 0.56, 95% CI 0.33-0.95) and intubation (relative risk 0.35, 95% CI 0.22-0.56) in both hypoxic and hypercapnic respiratory failure, but may have no effect on duration of NIV. There was an uncertain effect of helmet NIV on ICU length of stay and development of pressure sores. Data from observational studies were consistent with the foregoing findings but of lower certainty. Based on low and very low certainty data, helmet NIV may reduce intubation compared to HFNC, but its effect on mortality is uncertain. CONCLUSIONS: Compared to facemask NIV, helmet NIV may reduce mortality and intubation; however, the effect of helmet NIV compared to HFNC remains uncertain.

Discordances Between Factors Associated With Withholding Extubation and Extubation Failure After a Successful Spontaneous Breathing Trial.

OBJECTIVES: To identify whether factors associated with withholding extubation in the ICU also predict the risk of extubation failure. DESIGN: Retrospective cohort study. SETTING: Eight medical-surgical ICUs in Toronto. PATIENTS: Adult patients receiving invasive mechanical ventilation, with a first successful spontaneous breathing trial within 28 days of initial ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary end point had three mutually exclusive levels, including: 1) withholding extubation after a successful spontaneous breathing trial, 2) extubation failure within 48 hours, and 3) successful extubation. Among 9,910 patients, 38% of patients were not extubated within 24 hours of their first successful spontaneous breathing trial. A total of 12.9% of patients who were promptly extubated failed within the next 48 hours. Several discrepancies were evident in the association of factors with risk of withholding extubation and extubation failure. Specifically, both age and female sex were associated with withholding extubation (odds ratio, 1.07; 95% CI, 1.03-1.11; and odds ratio, 1.13; 95% CI, 1.02-1.26, respectively) but not a higher risk of failed extubation (odds ratio, 0.99; 95% CI, 0.93-1.05; and odds ratio, 0.93; 95% CI, 0.77-1.11, respectively). Conversely, both acute cardiovascular conditions and intubation for hypoxemic respiratory failure were associated with a higher risk of failed extubation (odds ratio, 1.32; 95% CI, 1.06-1.66; and odds ratio, 1.46; 95% CI, 1.16-1.82, respectively) but not a higher odds of a withheld extubation attempt (odds ratio, 0.79; 95% CI, 0.68-0.91; and odds ratio, 1.07; 95% CI, 0.93-1.23, respectively). CONCLUSIONS: Several factors showed discordance between the decision to withhold extubation and the risk of extubation failure. This discordance may lead to longer duration of mechanical ventilation or higher reintubation rates. Improving the decision-making behind extubation may help to reduce both exposure to invasive mechanical ventilation and extubation failure.

High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure.

PURPOSE: Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19. METHODS: We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding. RESULTS: Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days) and a reduction in ICU length of stay (mean difference: - 8.2 days; 95% CI - 12.7 to - 3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64). CONCLUSIONS: The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.

Compliance With Evidence-Based Processes of Care After Transitions Between Staff Intensivists.

OBJECTIVES: We sought to evaluate the impact of transitions of care among staff intensivists on the compliance with evidence-based processes of care. DESIGN: Cohort study using data from the Toronto Intensive Care Observational Registry. SETTING: Seven academic ICUs in Toronto, Ontario. PATIENTS: Critically ill mechanically ventilated adult patients. INTERVENTIONS: We explored the effects of the weekly transition of care among staff intensivists on compliance with three evidence-based processes of care (spontaneous breathing trials, lung-protective ventilation, and neuromuscular blocking agents). Two practices that are less guided by evidence (early discontinuation of antibiotics and extubation attempts) served as positive controls. We conducted the analysis using generalized estimating equations to account for clustering at the patient level. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 10,570 patients admitted between June 2014 and August 2018. Compliance varied for each practice (63.6%, 42.5%, and 21.1% for lung-protective ventilation, spontaneous breathing trials, and neuromuscular blockade, respectively). There was no effect of transitions of care on compliance with spontaneous breathing trials (odds ratio, 1.00; 95% CI, 0.95-1.07), lung-protective ventilation (odds ratio, 1.07, 95% CI, 0.90-1.26), or neuromuscular blockade use (odds ratio, 0.95; 95% CI, 0.75-1.20). However, early antibiotic discontinuation was more likely (odds ratio, 1.23; 95% CI, 1.06-1.42) and extubation attempts were less frequent (odds ratio, 0.77; 95% CI, 0.65-0.93) after a transition of care. CONCLUSIONS: We observed no significant impact of transitions of care between individual staff physicians on evidence-based processes of care for mechanically ventilated adult patients. However, transitions were associated with a lower likelihood of extubation and higher odds of earlier discontinuation of antibiotics.

Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis.

Importance: Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure. Objective: To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure. Data Sources: The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race. Study Selection: Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy. Data Extraction and Synthesis: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings. Main Outcomes and Measures: The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days. Results: Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 [95% CrI, 0.24-0.63]; absolute risk difference, -0.19 [95% CrI, -0.37 to -0.09]; low certainty) and face mask noninvasive ventilation (RR, 0.83 [95% CrI, 0.68-0.99]; absolute risk difference, -0.06 [95% CrI, -0.15 to -0.01]; moderate certainty) were associated with a lower risk of mortality (21 studies [3370 patients]). Helmet noninvasive ventilation (RR, 0.26 [95% CrI, 0.14-0.46]; absolute risk difference, -0.32 [95% CrI, -0.60 to -0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, -0.12 [95% CrI, -0.25 to -0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, -0.11 [95% CrI, -0.27 to -0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high. Conclusions and Relevance: In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.

Antiepileptic Drugs to Prevent Seizures After Spontaneous Intracerebral Hemorrhage.

Background and Purpose- We sought to evaluate the available literature to determine whether primary seizure prevention with antiepileptic drugs reduces the risk of poor outcomes and clinically relevant seizures among adult patients with spontaneous intracerebral hemorrhage. Methods- Meta-analysis of observational studies and randomized controlled trials evaluating the use of any antiepileptic drug for primary seizure prevention among adult (≥18 years) patients with spontaneous intracerebral hemorrhage. The primary end point was poor clinical outcome at the longest recorded follow-up, defined as either a high (>3) modified Rankin Scale score or all-cause mortality during follow-up if the modified Rankin Scale score was not recorded. Early and late seizures were secondary outcomes. A random mixed effects model was used to estimate the pooled odds ratio of outcomes and associated 95% CI. Results- We identified 7 studies with a total of 3241 patients for analysis of the primary outcome and 4 studies with a total of 1861 patients for analysis of the secondary outcomes. Overall, the use of antiepileptic drugs was not associated with a high Rankin Scale or all-cause mortality (odds ratio: 0.99; 95% CI, 0.66-1.49) or incident seizures (odds ratio: 0.89; 95% CI, 0.52-1.51) at the longest recorded follow-up time. Conclusions- The use of antiepileptic drugs as primary prevention among adult patients with spontaneous intracerebral hemorrhage is not associated with improved neurological function during long-term follow-up. Future studies should focus on the preventive use of distinct antiepileptic agents among patients at high risk of both seizures and poor outcomes.

Defining standard of practice: pros and cons of the usual care arm.

PURPOSE OF REVIEW: The aim of this review is to describe the use of usual care arms in randomized trials. RECENT FINDINGS: Randomization of patients to an experimental or a control arm remains paramount for the estimation of average causal effects. Selection of the control arm is as important as the definition of the intervention, and it might include a placebo control, specific standards of care, protocolized usual care, or unrestricted clinical practice. Usual care control arms may enhance generalizability, clinician acceptability of the protocol, patient recruitment, and ensure community equipoise, while at the same time introducing significant variability in the care delivered in the control group. This effect may reduce the difference in treatments delivered between the two groups and lead to a negative result or the requirement for a larger sample size. Moreover, usual care control groups can be subject to changes in clinician behavior induced by the trial itself, or by secular trends in time. SUMMARY: Usual care control arms may enhance generalizability while introducing significant limitations. Potential solutions include the use of pretrial surveys to evaluate the extent to which a protocolized control arm reflects the current standard of care and the implementation of adaptive trials.

Outcomes of hematopoietic cell transplant recipients requiring invasive mechanical ventilation: a two-centre retrospective cohort study.

PURPOSE: Outcomes of critically ill, hematopoietic cell transplant patients who require prolonged mechanical ventilation are not well studied. We describe the baseline characteristics, critical care management, and outcomes of this population and explore potential predictors of mortality. METHODS: We performed a retrospective cohort study in two critical care units in Ontario. We included adult intensive care unit patients who required invasive mechanical ventilation within 90 days of receiving a hematopoietic cell transplant. The primary outcome was mortality at 90 days. Using logistic regression, we explored predictors of mortality including type of transplant (allogeneic vs autologous), severity of illness (assessed using the Sequential Organ Failure Assessment [SOFA] score), and baseline characteristics (such as age and sex). RESULTS: We included 70 patients from two study sites. Ninety-day mortality was 73% (n = 51) in the entire cohort, 58% (15/26) in patients post-autologous transplant, and 82% (36/44) in those post-allogeneic transplant. Ninety-one percent (10/11) of patients who required invasive mechanical ventilation for more than 21 days died. Independent predictors of all-cause mortality included allogeneic transplant, higher SOFA score, the presence of acute hypoxemic respiratory failure, and a longer interval between receiving the transplant and initiation of mechanical ventilation. CONCLUSIONS: Our study shows high rates of mortality among hematopoietic cell transplant recipients that require invasive mechanical ventilation, particularly in those post-allogeneic transplant and in those who require prolonged ventilation for more than 21 days.

Antipsychotic Use Among Adult Outpatients and Venous Thromboembolic Disease: A Retrospective Cohort Study.

BACKGROUND: Treatment with antipsychotic (AP) agents is associated with incident thromboembolic events. However, the underpinnings of this association remain unknown. We sought to evaluate the effect of AP agents-categorized by their metabolic/sedative and hyperprolactinemia adverse effect profile-on the risk of venous thromboembolic disease during long-term follow-up. METHODS: A retrospective cohort study of adult patients initiating AP treatment for the first time was conducted. Primary outcome was defined as the time to venous thromboembolism (VTE) (either deep venous thrombosis or acute pulmonary embolism). Antipsychotic agents were categorized by their risk (high vs low) of either drug-induced (a) sedation/metabolic adverse event or (b) hyperprolactinemia. We used a propensity score-adjusted Cox proportional hazards model to control for confounding. FINDINGS: One thousand eight patients (mean age, 72.4 y) were followed for a median of 36 months. Incident VTE occurred in 6.25% of patients, corresponding to an incidence rate of 184 cases per 10,000 person-years. We found no difference in the hazard of VTE during follow-up between high- and low-risk groups (hazard ratio, 1.23 [95% confidence interval, 0.74-2.04] for drug-induced sedation/metabolic adverse event risk categories, and hazard ratio 0.81 [95% confidence interval, 0.50-1.35] for high versus low hyperprolactinemia risk). CONCLUSIONS: These results suggest that the risk of thromboembolic events in older adults who started AP treatment for the first time does not seem to be related to these drugs' risk of either sedation/metabolic adverse events or hyperprolactinemia. However, VTE remains a common problem in this subgroup of patients.