Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Awake prone positioning in adults with COVID-19

Importance: The impact of awake prone positioning (APP) on clinical outcomes in patients with COVID-19 and acute hypoxemic respiratory failure (AHRF) remains uncertain. Objective: To assess the association of APP with improved clinical outcomes among patients with COVID-19 and AHRF, and to identify potential effect modifiers. Data Sources: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through August 1, 2024. Study Selection: Randomized clinical trials (RCTs) examining APP in adults with COVID-19 and AHRF that reported intubation rate or mortality were included. Data Extraction and Synthesis: Individual participant data (IPD) were extracted according to PRISMA-IPD guidelines. For binary outcomes, logistic regression was used and odds ratio (OR) and 95% CIs were reported, while for continuous outcomes, linear regression was used and mean difference (MD) and 95% CIs were reported. Main Outcomes and Measures: The primary outcome was survival without intubation. Secondary outcomes included intubation, mortality, death without intubation, death after intubation, escalation of respiratory support, intensive care unit (ICU) admission, time from enrollment to intubation and death, duration of invasive mechanical ventilation, and hospital and ICU lengths of stay. Results: A total of 14 RCTs involving 3019 patients were included; 1542 patients in the APP group (mean [SD] age, 59.3 [14.1] years; 1048 male [68.0%]) and 1477 in the control group (mean [SD] age, 59.9 [14.1] years; 979 male [66.3%]). APP improved survival without intubation (OR, 1.42; 95% CI, 1.20-1.68), and it reduced the risk of intubation (OR, 0.70; 95% CI, 0.59-0.84) and hospital mortality (OR, 0.77; 95% CI, 0.63-0.95). APP also extended the time from enrollment to intubation (MD, 0.93 days; 95% CI, 0.43 to 1.42 days). In exploratory subgroup analyses, improved survival without intubation was observed in patients younger than age 68 years, as well as in patients with a body mass index of 26 to 30, early implementation of APP (ie, less than 1 day from hospitalization), a pulse saturation to inhaled oxygen fraction ratio of 155 to 232, respiratory rate of 20 to 26 breaths per minute (bpm), and those receiving advanced respiratory support at enrollment. However, none of the subgroups had significant interaction with APP treatment. APP duration 10 or more hours/d within the first 3 days was associated with increased survival without intubation (OR, 1.85; 95% CI, 1.37-2.49). Conclusions and Relevance: This IPD meta-analysis found that in adults with COVID-19 and AHRF, APP was associated with increased survival without intubation and with reduced risks of intubation and mortality, including death after intubation. Prolonged APP duration (10 or more hours/d) was associated with better outcomes

Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19

Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline. Conclusions and Relevance Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs. Trial Registration ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT0437258

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Operationalisation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 trials in a low and lower-middle income critical care learning health system.

The Randomized Embedded Multifactorial Adaptive Platform (REMAP-CAP) adapted for COVID-19) trial is a global adaptive platform trial of hospitalised patients with COVID-19. We describe implementation in three countries under the umbrella of the Wellcome supported Low and Middle Income Country (LMIC) critical  care network: Collaboration for Research, Implementation and Training in Asia (CCA). The collaboration sought to overcome known barriers to multi centre-clinical trials in resource-limited settings. Methods described focused on six aspects of implementation: i, Strengthening an existing community of practice; ii, Remote study site recruitment, training and support; iii, Harmonising the REMAP CAP- COVID trial with existing care processes; iv, Embedding REMAP CAP- COVID case report form into the existing CCA registry platform, v, Context specific adaptation and data management; vi, Alignment with existing pandemic and critical care research in the CCA. Methods described here may enable other LMIC sites to participate as equal partners in international critical care trials of urgent public health importance, both during this pandemic and beyond.</ns3:p

Implementing an intensive care registry in India: Preliminary results of the case-mix program and an opportunity for quality improvement and research

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%. Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research

Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%.  Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research.</ns4:p

Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%.  Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research.</ns4:p

Awake Prone Positioning in Adults With COVID-19: An Individual Participant Data Meta-Analysis

Importance: The impact of awake prone positioning (APP) on clinical outcomes in patients with COVID-19 and acute hypoxemic respiratory failure (AHRF) remains uncertain. Objective: To assess the association of APP with improved clinical outcomes among patients with COVID-19 and AHRF, and to identify potential effect modifiers. Data sources: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through August 1, 2024. Study selection: Randomized clinical trials (RCTs) examining APP in adults with COVID-19 and AHRF that reported intubation rate or mortality were included. Data extraction and synthesis: Individual participant data (IPD) were extracted according to PRISMA-IPD guidelines. For binary outcomes, logistic regression was used and odds ratio (OR) and 95% CIs were reported, while for continuous outcomes, linear regression was used and mean difference (MD) and 95% CIs were reported. Main outcomes and measures: The primary outcome was survival without intubation. Secondary outcomes included intubation, mortality, death without intubation, death after intubation, escalation of respiratory support, intensive care unit (ICU) admission, time from enrollment to intubation and death, duration of invasive mechanical ventilation, and hospital and ICU lengths of stay. Results: A total of 14 RCTs involving 3019 patients were included; 1542 patients in the APP group (mean [SD] age, 59.3 [14.1] years; 1048 male [68.0%]) and 1477 in the control group (mean [SD] age, 59.9 [14.1] years; 979 male [66.3%]). APP improved survival without intubation (OR, 1.42; 95% CI, 1.20-1.68), and it reduced the risk of intubation (OR, 0.70; 95% CI, 0.59-0.84) and hospital mortality (OR, 0.77; 95% CI, 0.63-0.95). APP also extended the time from enrollment to intubation (MD, 0.93 days; 95% CI, 0.43 to 1.42 days). In exploratory subgroup analyses, improved survival without intubation was observed in patients younger than age 68 years, as well as in patients with a body mass index of 26 to 30, early implementation of APP (ie, less than 1 day from hospitalization), a pulse saturation to inhaled oxygen fraction ratio of 155 to 232, respiratory rate of 20 to 26 breaths per minute (bpm), and those receiving advanced respiratory support at enrollment. However, none of the subgroups had significant interaction with APP treatment. APP duration 10 or more hours/d within the first 3 days was associated with increased survival without intubation (OR, 1.85; 95% CI, 1.37-2.49). Conclusions and relevance: This IPD meta-analysis found that in adults with COVID-19 and AHRF, APP was associated with increased survival without intubation and with reduced risks of intubation and mortality, including death after intubation. Prolonged APP duration (10 or more hours/d) was associated with better outcomes.No embarg