Objective:To evaluate the suitability of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU) for use in critical care registries across multiple continents. Design:A federated external validation study. Setting:Intensive care units (ICUs) belonging to 12 critical care registries on five continents. Participants:Individuals over the age of 18 years who were admitted to participating ICUs during the 2023 calendar year. Readmissions within the same hospital encounter and interhospital transfers were excluded. Interventions:None. Main outcome measures:The primary outcome was all-cause in-hospital mortality. A secondary analysis considered ICU mortality. Results:12 registries participated (three from Africa, four from Asia, one from Oceania, two from Europe and two from South America). In total, 494,705 admissions were included from 546 ICUs in 13 countries. Seven registries systematically reported hospital outcomes and were included in the primary analysis. Discrimination was acceptable (pooled area under the receiver operating characteristic curve [AUROC] 0.76 [95% CI 0.72-0.80]). Calibration and overall model fit varied between registries (Brier scores 0.09-0.14). In the secondary analysis of ICU outcomes in all 12 registries, discrimination remained acceptable but with higher variation between registries (pooled AUROC 0.73 [0.69-0.77]). Calibration and overall model fit also varied widely (Brier scores 0.07-0.46). Conclusions:SMS-ICU may be used as an index of illness severity in international intensive care populations. This may facilitate international collaborative research and synthesis of findings in systematic reviews and meta-analyses.

Objective: To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19.Design: An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.Setting: Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.Patients: Critically and noncritically ill patients.Interventions: Randomized to ivermectin or no ivermectin (control).Measurements and Main Results: 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. Analyses used a Bayesian cumulative logistic model. Enrollment was closed for operational futility, following external evidence suggesting no benefit with ivermectin in nonhospitalized patients with COVID-19. Among 61 critically ill patients, the median number of organ support-free days was -1, indicating death was the most common vital outcome (interquartile range [IQR], -1 to 17), for the ivermectin group and -1 (IQR, -1 to 17.25) for the control group (adjusted proportional odds ratio [OR], 0.94; 95% credible interval [CrI], 0.40-2.07) and the posterior probability of superiority to control was 44.2%. Among 89 noncritically ill patients, the median number of organ support-free days was 22 (IQR, 18.5-22) for ivermectin and 22 (IQR, 16-22) for control (adjusted proportional OR, 1.04; 95% CrI, 0.48-2.34) and the posterior probability of superiority was 53.7%. Among critically ill patients, hospital survival was 35.1% (13/37) for ivermectin and 37.5% (9/24) for control (adjusted OR, 1.00; 95% CrI, 0.39-2.32), posterior probability of superiority was 50.0%. Among noncritically ill patients, hospital survival was 84.1% (37/44) for ivermectin and 77.8% (35/45) for control (adjusted OR, 1.16; 95% CrI, 0.5-3.07), posterior probability of superiority was 63.3%.Conclusions: For critically and noncritically ill hospitalized patients with COVID-19, ivermectin was unlikely to improve the primary composite outcome of organ support-free days and hospital survival.

BACKGROUND:Intensive care unit registries, which aim to improve the quality of intensive care unit care through benchmarking and quality improvement initiatives, are active worldwide, with considerable dishomogeneity. We aimed to map core datasets, additional variables, and research activities of these registries. METHODS:A cross-sectional survey was disseminated to registry leads between October 2023 and June 2024. The survey was structured into four main topics: registry characteristics and coverage, core dataset features, additional modules, and registry-enabled research. RESULTS:Leads of 34/42 national registries responded (response rate 81%), covering 3,337 intensive care units, with a larger representation from South America. Systematized nomenclature of medicine, clinical terms, and customized categorical classifications were the main nomenclatures used. All registries except one employed a severity of illness score/risk prediction model. The SOFA score was reported by 88% of registries. Organ support measures were often recorded, including mechanical ventilation (97%), vasopressor administration (86%) and renal replacement therapy (86%). Three out of four intensive care unit registries coded interventions such as intubations, intravenous lines and tracheostomies. Additional datasets differed, with many use cases for nosocomial infection burden, bed availability and staffing resources. Over half of intensive care unit registries had current structured quality improvement initiatives. Registry-enabled observational research was reported in 46% of registries, while interventional studies were reported in only 22%. CONCLUSION:Over three thousand intensive care units in 35 countries participate in an intensive care unit registry. Despite heterogeneity in coding systems, risk models, and additional datasets, we identify several areas of convergence that may inform a future shared core dataset. There is potential for further intensive care unit registry-based research, particularly interventional.

BACKGROUND:The optimal thromboprophylaxis among critically ill adults with COVID-19 is uncertain. OBJECTIVES:To determine the effectiveness and safety of intermediate-dose heparin compared with standard low-dose thromboprophylaxis. METHODS:In an ongoing adaptive platform trial (randomized embedded multifactorial adaptive platform for community-acquired pneumonia), critically ill patients with COVID-19 were randomized to intermediate-dose heparin or standard low-dose thromboprophylaxis. Interventions were continued in hospital for up to 14 days. The primary endpoint was organ support-free days (OSFDs), an ordinal outcome combining in-hospital survival and the number of days free of intensive care unit-based respiratory or cardiovascular organ support through 21 days. The primary analysis was an adjusted Bayesian hierarchical cumulative logistic model. An odds ratio (OR) > 1.0 represents an improved outcome with intermediate-dose heparin. RESULTS:Between April 27, 2021 and November 25, 2023, 1255 critically ill adults with COVID-19 were enrolled from 78 sites in 15 countries, of whom 1254 completed follow-up (n = 572 intermediate-dose, n = 682 low-dose). Enrollment was terminated prior to reaching a prespecified statistical trigger due to declining case numbers and slow recruitment. Median age was 59 years, and 36.7% were female (n = 461/1255). The probability that intermediate-dose heparin improved OSFDs was 73.5% (OR, 1.06; 95% credible interval, 0.87, 1.30), which did not meet the prespecified superiority threshold of 99%. Hospital survival was 77.1% (441/572) and 76.7% (523/682) in the intermediate- and low-dose heparin groups, respectively (median adjusted OR, 1.14; 95% credible interval, 0.86, 1.52). Major bleeding occurred in 10 of 572 (1.7%) and 14 of 682 (2.1%) patients receiving intermediate and standard low doses, respectively. CONCLUSION:Intermediate-dose heparin did not improve OSFDs or survival compared with standard thromboprophylaxis in critically ill patients with COVID-19. (ClinicalTrials.gov number: CT02735707).

Background Almost all large-scale trials of disease-modifying therapeutic agents in critical care have failed to show benefit for patients, which may be explained in part by the clinical and biological heterogeneity inherent in virtually all critical illness syndromes. Enrichment strategies have been developed to separate responders from non-responders and better target treatments. In patients with the acute respiratory distress syndrome, a critical illness syndrome involving severe lung inflammation, latent class analysis and other clustering approaches have led to the discovery of subgroups (phenotypes) that appear to respond differently to treatment based on retrospective analyses of published clinical trials and observational cohorts. The next step is to test these phenotypes in a prospective trial. Rapid, point-of-care analytical methods have now made such a trial possible. There is a need to advance treatment for patients with acute respiratory distress syndrome and other critical illness syndromes by incorporating a phenotype-based approach into prospective trial design. The hyperinflammatory and hypoinflammatory phenotypes, that have been identified in acute respiratory distress syndrome, will be the first to be included in such a trial, with scope for further phenotypes to be studied over time. Future work This Efficacy and Mechanism Evaluation report, through expert consensus, describes a new Phase II, multiarm, adaptive platform randomised controlled trial design that tests multiple pharmacological therapies in a population of patients with acute respiratory distress syndrome stratified by baseline inflammatory phenotype. This report also reviews issues to be considered in developing precision medicine trials in critical care, which are designed with newly developed clinical phenotypes in mind. This work has been used to develop the Precision medicine Adaptive Network platform Trial in Hypoxaemic acutE respiratory failuRe precision medicine trial in acute respiratory distress syndrome, which has been funded and will begin recruitment in June 2025. Limitations This report is the result of expert consensus review, rather than utilising strict review methodologies (e.g. Delphi consensus process). However, expert consensus has been found to generate similar results to consensus processes when a high degree of agreement is reached and > 70% agreement was reached for all included recommendations. Funding This article presents independent research funded by the (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR154493.

BACKGROUND:Approximately half of all antimicrobial prescriptions in intensive care units (ICUs) may be inappropriate, including those prescribed when not needed, in unnecessary combinations or for longer durations than needed. Inappropriate prescribing is costly, exposes patients to unnecessary side-effects and drives population-level antimicrobial resistance, the prevalence and consequences of which are greatest in low- and middle-income countries. However, the implementation of interventions to improve the appropriateness of antimicrobial prescribing has been variable and requires further study. METHODS:We propose a type III hybrid implementation/effectiveness interventional cohort trial in 35 ICUs in up to 11 low- and middle- income countries. The study intervention is a structured review of antimicrobial prescriptions as recommended by the World Health Organisation. Strategies to support stakeholder-led implementation include development of local protocols, registry-enabled audit and feedback, and education. Evaluation of implementation, and the determinants of its success, is informed by the RE-AIM framework and the Consolidated Framework for Implementation Research respectively. The primary outcome is a composite measure of fidelity, reach and adoption. Secondary outcomes describe the effectiveness of the intervention on improving antimicrobial prescribing. Qualitative interviews will assess relevant implementation acceptability, adaptations and maintenance. A baseline survey will investigate ICU-level antimicrobial stewardship structures and processes. DISCUSSION:This study addresses global policy priorities by supporting implementation research of antimicrobial stewardship, and strengthening associated healthcare professional competencies. It does this in a setting where improvement is sorely needed: low- and middle- income country ICUs. The study will also describe the influence of pre-existing antimicrobial stewardship structures and processes on implementation and improve understanding about the efficacy of strategies to overcome barriers to implementation in these settings. TRIAL REGISTRATION:This study protocol has been registered with ClinicalTrials.gov (ref NCT06666738) on 31 Oct 2004. https://clinicaltrials.gov/study/NCT06666738?term=NCT06666738&rank=1 .

OBJECTIVE:To identify modifiable intensive care unit factors associated with outcomes among patients receiving invasive mechanical ventilation in a low-income setting. METHODS:This prospective, multicenter, registry-embedded observational study has two components: a prospective registry-based cohort assessing patient- and care-process-related factors and a cross-sectional intensive care unit survey evaluating organizational structure. Functional intensive care units in Uganda will be included. Patients aged ≥ 15 years old requiring invasive mechanical ventilation will be enrolled. Patients extubated within 48 hours, transferred after > 24 hours, and imminent early death will be excluded. Primary outcomes will include 28-day intensive care unit mortality, intensive care unit length of stay, and mechanical ventilation duration. Tracheostomy-related outcomes will be explored in a pre-planned sub-study. Factors potentially associated with outcomes will be categorized into non-modifiable and potentially modifiable factors. Non-modifiable factors will include patient-related factors like age, comorbidities, and illness severity; potentially modifiable factors include processes of care (e.g., sedation levels) and intensive care unit organizational structure (e.g., staffing patterns). Multilevel multivariable logistic regression models will assess association outcomes. Survival analysis (Kaplan-Meier curves) will explore mortality trends. Confounders will be identified using directed acyclic graphs. RESULTS (ANTICIPATED FINDINGS):This study will generate high-quality data on modifiable intensive care unit factors associated with ventilated patient outcomes in low-resource settings. CONCLUSION:This is Uganda's first registry-embedded, multicenter intensive care unit study to systematically potentially modifiable factors associated with ventilated patient outcomes. This study will provide evidence-based insights to optimize critical care management in low- and middle-income countries by leveraging real-time intensive care unit registry data.

INTRODUCTION:Tocilizumab improves outcomes in critically ill patients with COVID-19. Whether other immune-modulator strategies are equally effective or better is unknown. METHODS:We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients. In this ongoing, adaptive platform trial in 133 sites in 9 countries, we randomly assigned patients with allocation ratios dependent on the number of interventions available at each site. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21 in survivors. The trial used a Bayesian statistical model with predefined triggers for superiority, inferiority, efficacy, equivalence or futility. RESULTS:Of 2274 critically ill participants enrolled between 25 March 2020 and 10 April 2021, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were 7 (IQR -1, 16), 9 (IQR -1, 17), 0 (IQR -1, 15) and 0 (IQR -1, 15) for tocilizumab, sarilumab, anakinra and control, respectively. Median adjusted ORs were 1.46 (95% credible intervals (CrI) 1.13, 1.87), 1.50 (95% CrI 1.13, 2.00) and 0.99 (95% CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra relative to control, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared with control. All treatments appeared safe. CONCLUSIONS:In critically ill patients with COVID-19, tocilizumab and sarilumab have equivalent effectiveness at reducing duration of organ support and death. Anakinra is not effective in this population. TRIAL REGISTRATION NUMBER:NCT02735707.

ProblemThere is limited information on the prevalence, clinical features and outcomes of pediatric patients admitted to adult intensive care units (ICUs) or high-dependency units (HDUs) in low and middle income countries (LMICs).ObjectiveTo evaluate the clinical characteristics and outcomes of critically ill children admitted to adult ICU or HDU in Kenya.MethodsWe conducted a registry–enabled study leveraging on data collected progressively in the Kenya Critical Care Registry comprising six ICUs and five HDUs. We included all consecutive encounters of patients younger than 18 years who were admitted to the study units from January 2021 to June 2022.OutcomesThe primary outcome was ICU or HDU mortality; secondary outcomes included clinical management, duration of invasive ventilation, length of stay in the ICU or HDU and risk factors for mortality.ResultsOf the 5012 ICU and HDU admissions, 466 (9.1%) were patients younger than 18 years. Their median age was 2.0 [0.4–9.0] years, with 173 (37.1%) children being under one year. Medical admissions accounted for 357 (76.6%) cases, while 109 (23.9%) were surgical. Almost half of the children received invasive ventilation, whereas noninvasive ventilation was rarely used. The use of cardiovascular support and renal replacement therapy was also uncommon. Approximately one quarter of children were sedated on admission, and more than 80% received at least one antibiotic. The overall ICU or HDU mortality rate was 34.5%, higher in medical cases than in surgical cases (39.5 vs. 18.3%, p < 0.001). Independent risk factors for mortality were age under 28 days, admission due to a medical reason and receiving invasive ventilation.ConclusionsIn a representative sample of Kenyan ICUs, one out of nine admissions to adult ICUs and HDUs involves a child, who often receive invasive ventilation and have a high crude mortality rate. In this cohort of patients, all risk factors for mortality were non-modifiable.

Background Awake prone positioning (APP) may be beneficial in patients with respiratory failure who are not receiving mechanical ventilation. Randomized controlled trials of APP have been performed during peak COVID-19 periods in unvaccinated populations, with limited data on compliance or patient acceptability. We aimed to evaluate the efficacy and acceptability of APP in a lower-middle income country in an open-label randomized controlled trial using a dedicated APP implementation team and wearable continuous-monitoring devices. Methods The trial was performed at a tertiary level hospital in Ho Chi Minh City, Vietnam, recruiting adults (≥18 years) hospitalized with moderate or severe COVID-19 and receiving supplemental oxygen therapy via nasal/facemask systems or high-flow nasal cannula (HFNC). Patients were allocated by a computer-generated random number sequence in a 1:1 ratio to standard care or APP, where a dedicated team provided bedside support. Wearable devices continuously recorded pulse oximetry and body position continuously. Our primary outcome was escalation of respiratory support within 28 days of randomization. Results Ninety-three patients were enrolled in this study between March 2022 and March 2023. Eighty (86%) patients had received ≥2 doses of SARS-CoV2 vaccine. The study was terminated early because of a reduction in the number of eligible patients. Data from 46 patients allocated to APP and 47 to standard care were available for analysis. At baseline, 19/47 (40%) patients allocated to the standard care group and 14/46 (30%) patients allocated to the APP group received HFNC. Continuous monitoring data were available for all patients monitored with wearable devices. Significantly greater mean daily APP times were achieved in those allocated to APP, however, most achieved less than the target 8 h/day. We did not detect clear differences in the primary outcome (relative risk,RR, 0.85, 95% CI 0.40-1.78, p=0.67) or secondary outcomes, including intubation rate and 28-day mortality. Patients reported prone positioning was comfortable, although almost all patients preferred supine positioning. No adverse events associated with the intervention were observed. Conclusions APP was not associated with benefit, but there was no sign of harm. Continuous monitoring with wearable devices is both feasible and acceptable for patients. In our population, achieving prolonged APP time was challenging despite a dedicated support team, and patients preferred supine positioning. Clinical Trials Registration NCT05083130.

Background The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with hypoxic ischaemic encephalopathy (HIE) following a cardiac arrest who are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective To summarise the protocol and statistical analysis plan for the Mega-ROX HIE trial. Design, setting and participants Mega-ROX HIE is an international randomised clinical trial that will be conducted within an overarching 40,000-participant registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol approximately 4000 participants with suspected HIE following a cardiac arrest who are receiving invasive mechanical ventilation in the ICU. Main outcome measures The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home. Results and conclusions Mega-ROX HIE will compare the effect of conservative vs. liberal oxygen therapy regimens on day-90 in-hospital mortality in adults in the ICU with suspected HIE following a cardiac arrest. The protocol and planned analyses are reported here to mitigate analysis bias. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

Background Awake prone positioning (APP) may be beneficial in patients with respiratory failure who are not receiving mechanical ventilation. Randomized controlled trials of APP have been performed during peak COVID-19 periods in unvaccinated populations, with limited data on compliance or patient acceptability. We aimed to evaluate the efficacy and acceptability of APP in a lower-middle income country in an open-label randomized controlled trial using a dedicated APP implementation team and wearable continuous-monitoring devices. Methods The trial was performed at a tertiary level hospital in Ho Chi Minh City, Vietnam, recruiting adults (≥18 years) hospitalized with moderate or severe COVID-19 and receiving supplemental oxygen therapy via nasal/facemask systems or high-flow nasal cannula (HFNC). Patients were allocated by a computer-generated random number sequence in a 1:1 ratio to standard care or APP, where a dedicated team provided bedside support. Wearable devices continuously recorded pulse oximetry and body position continuously. Our primary outcome was escalation of respiratory support within 28 days of randomization. Results Ninety-three patients were enrolled in this study between March 2022 and March 2023. Eighty (86%) patients had received ≥2 doses of SARS-CoV2 vaccine. The study was terminated early because of a reduction in the number of eligible patients. Data from 46 patients allocated to APP and 47 to standard care were available for analysis. At baseline, 19/47 (40%) patients allocated to the standard care group and 14/46 (30%) patients allocated to the APP group received HFNC. Continuous monitoring data were available for all patients monitored with wearable devices. Significantly greater mean daily APP times were achieved in those allocated to APP, however, most achieved less than the target 8 h/day. We did not detect clear differences in the primary outcome (relative risk,RR, 0.85, 95% CI 0.40-1.78, p=0.67) or secondary outcomes, including intubation rate and 28-day mortality. Patients reported prone positioning was comfortable, although almost all patients preferred supine positioning. No adverse events associated with the intervention were observed. Conclusions APP was not associated with benefit, but there was no sign of harm. Continuous monitoring with wearable devices is both feasible and acceptable for patients. In our population, achieving prolonged APP time was challenging despite a dedicated support team, and patients preferred supine positioning. Clinical Trials Registration NCT05083130.

BackgroundLower limb amputation (LLA) impacts physical activity (PA) participation and quality of life (QoL). To minimize the effects of these challenges, LLA survivors need to have opportunities to engage in appropriately tailored rehabilitation throughout their lives. However, in Sri Lanka, where a 3-decade civil war resulted in trauma-related LLA among young male soldiers, access to rehabilitation was limited to the immediate postinjury period. Developing rehabilitation interventions for these veterans requires an understanding of their current health status and rehabilitation perceptions. ObjectiveThis study was conducted to evaluate the QoL and PA participation of veterans with LLA and explore perceptions of factors influencing their PA participation and expectations for a future community-based physical rehabilitation (CBPR) intervention. MethodsThis mixed methods study combined a comparative cross-sectional quantitative survey with qualitative semistructured interviews in 5 districts of Sri Lanka. QoL and PA participation were assessed among community-reintegrated veterans with LLA (n=85) and compared with a matched able-bodied cohort (control; n=85) using Mann-Whitney U and Chi-square tests. PA was assessed in terms of metabolic equivalent of task (MET) minutes per week and was computed for walking, moderate-intensity, and vigorous-intensity activities. PA was classified as sufficiently active, low, or sedentary. The design of interview questions was guided by the Theoretical Domains Framework and followed a phenomenological approach. Interviews were conducted with 25 veterans and were analyzed thematically, and the perceptions regarding PA participation and CBPR were codified using the Consolidated Framework for Implementation Research (CFIR). ResultsBased on the quantitative survey findings, scores for both physical (P<.001) and psychological (P<.001) well-being and participation in walking (P=.004) and vigorous-intensity activities (P<.001) were significantly lower among veterans than among controls. A “sedentary” classification was made for 43% (34/79) of veterans and 12% (10/82) of controls. Veterans mostly engaged in moderate-intensity PA inside the house (49/79, 62%) and in the yard (30/79, 38%). Qualitative interviews revealed that barriers to PA exist at individual (eg, comorbidity burden), primary care (eg, absence of community rehabilitation services), and policy levels (eg, limited resources) and facilitators exist primarily at societal (eg, inclusive community) and individual levels (eg, preinjury activity baseline and positive attitudes toward exercise). Expectations regarding CBPR included individualized rehabilitation parameters; functional exercises; and involvement of peers, amputee societies, and community health care providers. The nonresponse rate for interviews was 7% (2/27). ConclusionsThe findings of reduced PA participation, poor QoL, and physical and psychological impairments among relatively young veterans reveal the long-term impacts of living with LLA in the absence of long-term rehabilitation. Policy-level changes need to be implemented along with behavior-change strategies to promote PA participation and minimize physical inactivity–induced health issues. Veterans’ perceptions regarding future CBPR programs were positive and centered on holistic, individualized, and peer-led activities.

Background The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. Methods We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. Findings Among 1642632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95%CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95%CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. Interpretation Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Background Awake prone positioning (APP) may be beneficial in patients with respiratory failure who are not receiving mechanical ventilation. Randomized controlled trials of APP have been performed during peak COVID-19 periods in unvaccinated populations, with limited data on compliance or patient acceptability. We aimed to evaluate the efficacy and acceptability of APP in a lower-middle income country in an open-label randomized controlled trial using a dedicated APP implementation team and wearable continuous-monitoring devices. Methods The trial was performed at a tertiary level hospital in Ho Chi Minh City, Vietnam, recruiting adults (≥18 years) hospitalized with moderate or severe COVID-19 and receiving supplemental oxygen therapy via nasal/facemask systems or high-flow nasal cannula (HFNC). Patients were allocated by a computer-generated random number sequence in a 1:1 ratio to standard care or APP, where a dedicated team provided bedside support. Wearable devices continuously recorded pulse oximetry and body position continuously. Our primary outcome was escalation of respiratory support within 28 days of randomization. Results Ninety-three patients were enrolled in this study between March 2022 and March 2023. Eighty (86%) patients had received ≥2 doses of SARS-CoV2 vaccine. The study was terminated early because of a reduction in the number of eligible patients. Data from 46 patients allocated to APP and 47 to standard care were available for analysis. At baseline, 19/47 (40%) patients allocated to the standard care group and 14/46 (30%) patients allocated to the APP group received HFNC. Continuous monitoring data were available for all patients monitored with wearable devices. Significantly greater mean daily APP times were achieved in those allocated to APP, however, most achieved less than the target 8 h/day. We did not detect clear differences in the primary outcome (relative risk,RR, 0.85, 95% CI 0.40-1.78, p=0.67) or secondary outcomes, including intubation rate and 28-day mortality. Patients reported prone positioning was comfortable, although almost all patients preferred supine positioning. No adverse events associated with the intervention were observed. Conclusions APP was not associated with benefit, but there was no sign of harm. Continuous monitoring with wearable devices is both feasible and acceptable for patients. In our population, achieving prolonged APP time was challenging despite a dedicated support team, and patients preferred supine positioning. Clinical Trials Registration NCT05083130.

OBJECTIVES:. To describe clinical, management, and outcome features of critically ill patients admitted to ICUs and high-dependency units (HDUs) in Kenya. DESIGN:. Prospective registry-based observational study. SETTING:. Three HDUs and eight ICUs in Kenya. PATIENTS:. Consecutive adult patients admitted between January 2021 and June 2022. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Data were entered in a cloud-based platform using a common data model. Study endpoints included case-mix variables, management features, and patient-centered outcomes. Patients with COVID-19 were reported separately. Of the 3892 of 4546 patients without COVID-19, 2445 patients (62.8%) were from HDUs, and 1447 patients (37.2%) were from ICUs. Patients had a median age of 53 years (interquartile range [IQR] 38–68), with HDU patients being older but with a lower severity (Acute Physiology and Chronic Health Evaluation II 6 [3–9] in HDUs vs. 12 [7–17] in ICUs; p < 0.001). One in four patients was postoperative with 604 (63.4%) receiving emergency surgery. Readmission rate was 4.8%. Hypertension and diabetes were prevalent comorbidities, with a 4.0% HIV/AIDS rate. Invasive mechanical ventilation was applied in 3.4% in HDUs versus 47.6% in ICUs (p < 0.001), with a duration of 7 days (IQR 3–21). There was a similar use of renal replacement therapy (4.0% vs. 4.7%; p < 0.001). Vasopressor use was infrequent while half of patients received antibiotics. Average length of stay was 2 days (IQR 1–5). Crude HDU mortality rate was 6.5% in HDUs versus 30.5% in the ICUs (p < 0.001). Of the 654 COVID-19 admissions, most were admitted in ICUs (72.3%) with a 33.2% mortality. CONCLUSIONS:. We provide the first multicenter observational cohort study from an African ICU National Registry. Distinct management features and outcomes characterize HDU from ICU patients.

Key Points Question: What is the burden of critical illness in hospitals in different global settings, and where are critically ill patients being cared for? Findings: Among 3652 hospitalized patients in countries of different socio-economic levels we found a point-prevalence of critical illness of 12% with a hospital mortality of 19%. Of the critically ill patients 96% were cared for in general wards. Meaning: Critical illness is common in hospitals and has a high mortality. Ensuring that feasible adequate critical care interventions are implemented throughout hospitals could impact a large number of high-risk patients and has potential to improve outcomes across all medical specialties. Abstract Importance: The burden of critical illness may have been underestimated and there is little data showing where critically ill patients receive care. Objective: To assess the adult burden of critical illness in hospitals across different global settings. Design, Setting, and Participants: This was a prospective, observational, hospital-based, point-prevalence and cohort study in Malawi, Sri Lanka and Sweden. On specific days, all adult in-patients in the eight study hospitals were examined by the study team for the presence of critical illness and followed up for hospital mortality. Exposure: Patients with at least one severely deranged vital sign were classified as critically ill. Main Outcomes and Measures: The primary study outcomes were the presence of critical illness and 30-day hospital mortality. In addition, we determined where in the hospitals the critically ill patients were being cared for and the association between critical illness and 30-day hospital mortality. Results: Among 3652 hospitalized patients in countries of different socio-economic levels we found a point-prevalence of critical illness of 12.0% (95% CI, 11.0-13.1), with a hospital mortality of 18.7% (95% CI, 15.3-22.6). The crude odds ratio of death of critically ill compared to non-critically ill patients was 7.5 (95% CI, 5.4-10.2). Of the critically ill patients 96.1% (95% CI, 93.9-97.6) were cared for in the general wards outside Intensive Care Units (ICUs). Conclusions and Relevance: The study has revealed a substantial burden of critical illness in hospitals from different global settings. One in eight hospital in-patients was critically ill, 19% of the critically ill died in hospital, and 96% of the critically ill patients were cared for outside of ICUs. Implementing fundamental low-cost critical care in units and general wards throughout hospitals could impact a large number of high-risk patients and has the potential to improve outcomes across all acute care specialties. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Centre for Clinical Research Sormland, Uppsala University, Sweden, Regional Research Council Mid Sweden, Swedish Research Council, the Association of Anaesthetists of Great Britain and Ireland, Travel Grants from Swedish Society of Medicine and Karolinska Institutet, Martin Rinds Stiftelse, Life Support Foundation and Laerdal Foundation. The funders had no role in study design, data collection and analysis, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees in all study settings gave ethical approval for this work. Malawi: College of Medicine Reserach and Ethics Committee (P.08/16/2007); Sri Lanka: Ethics Review Committee, Faculty of Medicine, University of Kelaniya (P/111/04/2018) and Ethics Review Committee, Faculty of Medicine, University of Jaffna (J/ERC/19/102/NDR/0205); Sweden: Ethical Review Board Stockholm (2017-1907-31-1). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Due to the sensitive nature of the information about severely unwell patients, and the requirements of the College of Medicine Research and Ethics Committee, data from the study are not publicly available. Data can be requested by contacting the corresponding author carl.schell@ki.se including a reasonable motivation for the request for the data and a study plan.

Background This study evaluates the predictive performance of prognostic models derived from low- and middle-income country (LMIC) data using a multinational Asian critical care dataset. The research also seeks to identify opportunities for improving these models' accuracy and utility in clinical research and for international benchmarking of critical care outcomes Methods This retrospective multicenter study evaluated the performance of four prognostic models: e-Tropical Intensive Care Score (e-TropICS), Tropical Intensive Care Score (TropICS), Simplified Mortality Score for the Intensive Care Unit (SMS-ICU), and Rwanda Mortality Probability Model (R-MPM) using a dataset of 64,327 ICU admissions from 109 ICUs across six Asian countries. The models' discriminative abilities were assessed using ROC curves, and calibration was evaluated with Hosmer-Lemeshow C-statistics and calibration curves. Recalibration was performed to improve model accuracy, and the impact of the COVID-19 pandemic on model performance was also analysed. Results The e-TropICS and R-MPM models showed relatively good discriminative power, with AUCs of 0.71 and 0.69, respectively. However, all models exhibited significant calibration issues, particularly at higher predicted probabilities, even after recalibration. The study also revealed variability in model performance across different countries, with India's data demonstrating the highest discriminative power. Conclusions The study highlights the challenges of applying existing prognostic models in diverse ICU settings, particularly in LMICs. While the e-TropICS and R-MPM models performed relatively well, significant calibration issues indicate a need for further refinement. Future efforts should focus on developing adaptable models that can effectively accommodate the diverse and dynamic nature of ICU populations worldwide, ensuring their utility in global healthcare benchmarking and decision-making.