The burden of anxiety, depression, and stress, along with the prevalence of symptoms of PTSD, and perceptions of the drivers of psychological harms, as perceived by doctors and nurses working in ICUs in Nepal during the COVID-19 pandemic; a mixed method evaluation.

BACKGROUND: The COVID-19 pandemic resulted in significant physical and psychological impacts for survivors, and for the healthcare professionals caring for patients. Nurses and doctors in critical care faced longer working hours, increased burden of patients, and limited resources, all in the context of personal social isolation and uncertainties regarding cross-infection. We evaluated the burden of anxiety, depression, stress, post-traumatic stress disorder (PTSD), and alcohol dependence among doctors and nurses working in intensive care units (ICUs) in Nepal and explored the individual and social drivers for these impacts. METHODS: We conducted a mixed-methods study in Nepal, using an online survey to assess psychological well-being and semi-structured interviews to explore perceptions as to the drivers of anxiety, stress, and depression. Participants were recruited from existing national critical care professional organisations in Nepal and using a snowball technique. The online survey comprised of validated assessment tools for anxiety, depression, stress, PTSD, and alcohol dependence; all tools were analysed using published guidelines. Interviews were analysed using rapid appraisal techniques, and themes regarding the drivers for psychological distress were explored. RESULTS: 134 respondents (113 nurses, 21 doctors) completed the online survey. Twenty-eight (21%) participants experienced moderate to severe symptoms of depression; 67 (50%) experienced moderate or severe symptoms of anxiety; 114 (85%) had scores indicative of moderate to high levels of stress; 46 out of 100 reported symptoms of PTSD. Compared to doctors, nurses experienced more severe symptoms of depression, anxiety, and PTSD, whereas doctors experienced higher levels of stress than nurses. Most (95%) participants had scores indicative of low risk of alcohol dependence. Twenty participants were followed up in interviews. Social stigmatism, physical and emotional safety, enforced role change and the absence of organisational support were perceived drivers for poor psychological well-being. CONCLUSION: Nurses and doctors working in ICU during the COVID-19 pandemic sustained psychological impacts, manifesting as stress, anxiety, and for some, symptoms of PTSD. Nurses were more vulnerable. Individual characteristics and professional inequalities in healthcare may be potential modifiable factors for policy makers seeking to mitigate risks for healthcare providers.

EPidemiology, clinical characteristics and Outcomes of 4546 adult admissions to high-dependency and intensive care units in Kenya (EPOK): a multicentre registry-based observational study.

Objective: to describe clinical, management and outcome features of critically ill patients admitted to intensive care units (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 was entered in a cloud based platform using a common data model. Study endpoints included case mix variables, management features and patient centred outcomes. Patients with Coronavirus disease 2019 (COVID-19) were reported separately. Of the 3892/4546 patients without COVID-19, 2445 patients (62.8%) were from HDUs and 1447 (37.2%) 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 (APACHE II 6 [3-9] in HDUs vs 12 [7-17] in ICUs; p<0.001). One out of four patients were 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 (IMV) was applied in 3.4% in HDUs vs. 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 characterise HDU from ICU patients. Study registration: Clinicaltrials.gov (reference number NCT05456217, date of registration 07 Nov 2022).

Implementing an ICU registry in Ethiopia-Implications for critical care quality improvement.

PURPOSE: Intensive care units (ICUs) in low- and middle-income countries have high mortality rates, and clinical data are needed to guide quality improvement (QI) efforts. This study utilizes data from a validated ICU registry specially developed for resource-limited settings to identify evidence-based QI priorities for ICUs in Ethiopia. MATERIALS AND METHODS: A retrospective cohort analysis of data from two tertiary referral hospital ICUs in Addis Ababa, Ethiopia from July 2021-June 2022 was conducted to describe casemix, complications and outcomes and identify features associated with ICU mortality. RESULTS: Among 496 patients, ICU mortality was 35.3%. The most common reasons for ICU admission were respiratory failure (24.0%), major head injury (17.5%) and sepsis/septic shock (13.3%). Complications occurred in 41.0% of patients. ICU mortality was higher among patients with respiratory failure (46.2%), sepsis (66.7%) and vasopressor requirements (70.5%), those admitted from the hospital ward (64.7%), and those experiencing major complications in the ICU (62.3%). CONCLUSIONS: In this study, ICU mortality was high, and complications were common and associated with increased mortality. ICU registries are invaluable tools to understand local casemix and clinical outcomes, especially in resource-limited settings. These findings provide a foundation for QI efforts and a baseline to evaluate their impact.

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

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 1 642 632 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.

Prevalence of frailty and association with patient centered outcomes: A prospective registry-embedded cohort study from India.

PURPOSE: We aimed to study the prevalence of frailty, evaluate risk factors, and understand impact on outcomes in India. METHODS: This was a prospective registry-embedded cohort study across 7 intensive care units (ICUs) and included adult patients anticipated to stay for at least 48 h. Primary exposure was frailty, as defined by a score ≥ 5 on the Clinical Frailty Scale and primary outcome was ICU mortality. Secondary outcomes included in-hospital mortality and resource utilization. We used generalized linear models to evaluate risk factors and model association between frailty and outcomes. RESULTS: 838 patients were included, with median (IQR) age 57 (42,68) yrs.; 64.8% were male. Prevalence of frailty was 19.8%. Charlson comorbidity index (OR:1.73 (95%CI:1.39,2.15)), Subjective Global Assessment categories mild/moderate malnourishment (OR:1.90 (95%CI:1.29, 2.80)) and severe malnourishment (OR:4.76 (95% CI:2.10,10.77)) were associated with frailty. Frailty was associated with higher odds of ICU mortality (adjusted OR:2.04 (95% CI:1.25,3.33)), hospital mortality (adjusted OR:2.36 (95%CI:1.45,3.84)), development of stage2/3 AKI (unadjusted OR:2.35 (95%CI:1.60, 3.43)), receipt of non-invasive ventilation (unadjusted OR:2.68 (95%CI:1.77, 4.03)), receipt of vasopressors (unadjusted OR:1.47 (95%CI:1.04, 2.07)), and receipt of kidney replacement therapy (unadjusted OR:3.15 (95%CI:1.90, 5.17)). CONCLUSIONS: Frailty is common among critically ill patients in India and is associated with worse outcomes. STUDY REGISTRATION: CTRI/2021/02/031503.

National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

Critical care bed capacity in Asian countries and regions before and during the COVID-19 pandemic: an observational study.

Background: The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of critical care. The aim of the current study was to compare the number of adult critical care beds in relation to population size in Asian countries and regions before (2017) and during (2022) the pandemic. Methods: This observational study collected data closest to 2022 on critical care beds (intensive care units and intermediate care units) in 12 middle-income and 7 high-income economies (using the 2022-2023 World Bank classification), through a mix of methods including government sources, national critical care societies, personal contacts, and data extrapolation. Data were compared with a prior study from 2017 of the same countries and regions. Findings: The cumulative number of critical care beds per 100,000 population increased from 3.0 in 2017 to 9.4 in 2022 (p = 0.003). The median figure for middle-income economies increased from 2.6 (interquartile range [IQR] 1.7-7.8) to 6.6 (IQR 2.2-13.3), and that for high-income economies increased from 11.4 (IQR 7.3-22.8) to 13.9 (IQR 10.7-21.7). Only 3 countries did not see a rise in bed capacity. Where data were available in 2022, 10.9% of critical care beds were in single rooms (median 5.0% in middle-income and 20.3% in high-income economies), and 5.3% had negative pressure (median 0.7% in middle-income and 18.5% in high-income economies). Interpretation: Critical care bed capacity in the studied Asian countries and regions increased close to three-fold from 2017 to 2022. Much of this increase was attributed to middle-income economies, but substantial heterogeneity exists. Funding: None.

Mixed methods study protocol for combining stakeholder-led rapid evaluation with near real-time continuous registry data to facilitate evaluations of quality of care in intensive care units.

Background: Improved access to healthcare in low- and middle-income countries (LMICs) has not equated to improved health outcomes. Absence or unsustained quality of care is partly to blame. Improving outcomes in intensive care units (ICUs) requires delivery of complex interventions by multiple specialties working in concert, and the simultaneous prevention of avoidable harms associated with the illness and the treatment interventions. Therefore, successful design and implementation of improvement interventions requires understanding of the behavioural, organisational, and external factors that determine care delivery and the likelihood of achieving sustained improvement. We aim to identify care processes that contribute to suboptimal clinical outcomes in ICUs located in LMICs and to establish barriers and enablers for improving the care processes. Methods: Using rapid evaluation methods, we will use four data collection methods: 1) registry embedded indicators to assess quality of care processes and their associated outcomes; 2) process mapping to provide a preliminary framework to understand gaps between current and desired care practices; 3) structured observations of processes of interest identified from the process mapping and; 4) focus group discussions with stakeholders to identify barriers and enablers influencing the gap between current and desired care practices. We will also collect self-assessments of readiness for quality improvement. Data collection and analysis will be led by local stakeholders, performed in parallel and through an iterative process across eight countries: Kenya, India, Malaysia, Nepal, Pakistan, South Africa, Uganda and Vietnam. Conclusions: The results of our study will provide essential information on where and how care processes can be improved to facilitate better quality of care to critically ill patients in LMICs; thus, reduce preventable mortality and morbidity in ICUs. Furthermore, understanding the rapid evaluation methods that will be used for this study will allow other researchers and healthcare professionals to carry out similar research in ICUs and other health services.

Simvastatin in Critically Ill Patients with Covid-19.

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

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with sepsis in the intensive care unit (Mega-ROX Sepsis).

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial. Design setting and participants: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial. 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 patients discharged home. Results and conclusions: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias.

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains).

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial. Design setting and participants: Mega-ROX Brains is an international randomised clinical trial, which 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 between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d 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 Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

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

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

Impact and burden of sickle cell disease in critically ill obstetric patients in a high dependency unit in Sierra Leone-a registry based evaluation.

INTRODUCTION: Sickle cell disease (SCD) in pregnancy is associated with worse maternal and neonatal outcomes. There is limited available data describing the burden and outcomes of critically ill obstetric patients affected by SCD in low-income settings. OBJECTIVES: We aimed to define SCD burden and impact on mortality in critically-ill obstetric patients admitted to an urban referral hospital in Sierra Leone. We hypothesized that SCD burden is high and independently associated with increased mortality. METHODS: We performed a registry-based cross-sectional study from March 2020 to December 2021 in the high-dependency unit (HDU) of Princess Christian Maternity Hospital PCMH, Freetown. Primary endpoints were the proportion of patients identified in the SCD group and HDU mortality. Secondary endpoints included frequency of maternal direct obstetric complications (MDOCs) and the maternal early obstetric warning score (MEOWS). RESULTS: Out of a total of 497 patients, 25 (5.5%) qualified to be included in the SCD group. MEOWS on admission was not different between patients with and without SCD and SCD patients had also less frequently reported MDOCs. Yet, crude HDU mortality in the SCD group was 36%, compared to 9.5% in the non SCD group (P < 0.01), with an independent association between SCD group exposure and mortality when accounting for severity on admission (hazard ratio 3.40; 95%CI 1.57-7.39; P = 0.002). Patients with SCD had a tendency to longer HDU length of stay. CONCLUSIONS: One out of twenty patients accessing a HDU in Sierra Leone fulfilled criteria for SCD. Despite comparable severity on admission, mortality in SCD patients was four times higher than patients without SCD. Optimization of intermediate and intensive care for this group of patients should be prioritized in low-resource settings with high maternal mortality.

Critical illness at the emergency department of a Tanzanian national hospital in a three-year period 2019-2021.

BACKGROUND: Critically ill patients have life-threatening conditions requiring immediate vital organ function intervention. But, critical illness in the emergency department (ED) has not been comprehensively described in resource-limited settings. Understanding the characteristics and dynamics of critical illness can help hospitals prepare for and ensure the continuum of care for critically ill patients. This study aimed to describe the pattern and outcomes of critically ill patients at the ED of the National Hospital in Tanzania from 2019 to 2021. METHODOLOGY: This hospital-records-based retrospective cohort study analyzed records of all patients who attended the ED of Muhimbili National Hospital between January 2019 and December 2021. Data extracted from the ED electronic database included clinical and demographic information, diagnoses, and outcome status at the ED. Critical illness in this study was defined as either a severe derangement of one or more vital signs measured at triage or the provision of critical care intervention. Data were analyzed using Stata 17 to examine critical illnesses' burden, characteristics, first-listed diagnosis, and outcomes at the ED. RESULTS: Among the 158,445 patients who visited the ED in the study period, 16,893 (10.7%) were critically ill. The burden of critical illness was 6,346 (10.3%) in 2019, 5,148 (10.9%) in 2020, and 5,400 (11.0%) in 2021. Respiratory (18.8%), cardiovascular (12.6%), infectious diseases (10.2%), and trauma (10.2%) were the leading causes of critical illness. Most (81.6%) of the critically ill patients presenting at the ED were admitted or transferred, of which 11% were admitted to the ICUs and 89% to general wards. Of the critically ill, 4.8% died at the ED. CONCLUSION: More than one in ten patients attending the Tanzanian National Hospital emergency department was critically ill. The number of critically ill patients did not increase during the pandemic. The majority were admitted to general hospital wards, and about one in twenty died at the ED. This study highlights the burden of critical illness faced by hospitals and the need to ensure the availability and quality of emergency and critical care throughout hospitals.

Organisation, staffing and resources of critical care units in Kenya.

OBJECTIVE: To describe the organisation, staffing patterns and resources available in critical care units in Kenya. The secondary objective was to explore variations between units in the public and private sectors. MATERIALS AND METHODS: An online cross-sectional survey was used to collect data on organisational characteristics (model of care, type of unit, quality- related activities, use of electronic medical records and participation in the national ICU registry), staffing and available resources for monitoring, ventilation and general critical care. RESULTS: The survey included 60 of 75 identified units (80% response rate), with 43% (n = 23) located in government facilities. A total of 598 critical care beds were reported with a median of 6 beds (interquartile range [IQR] 5-11) per unit, with 26% beds (n = 157) being non functional. The proportion of ICU beds to total hospital beds was 3.8% (IQR 1.9-10.4). Most of the units (80%, n = 48) were mixed/general units with an open model of care (60%, n = 36). Consultants-in-charge were mainly anesthesiologists (69%, n = 37). The nurse-to-bed ratio was predominantly 1:2 with half of the nurses formally trained in critical care. Most units (83%, n = 47) had a dedicated ventilator for each bed, however 63% (n = 39) lacked high flow nasal therapy. While basic multiparametric monitoring was ubiquitous, invasive blood pressure measurement capacity was low (3% of beds, IQR 0-81%), and capnography moderate (31% of beds, IQR 0-77%). Blood gas analysers were widely available (93%, n = 56), with 80% reported as functional. Differences between the public and private sector were narrow. CONCLUSION: This study shows an established critical care network in Kenya, in terms of staffing density, availability of basic monitoring and ventilation resources. The public and private sector are equally represented albeit with modest differences. Potential areas for improvement include training, use of invasive blood pressure and functionality of blood gas analysers.

Correction: The burden of respiratory conditions in the emergency department of Muhimbili National Hospital in Tanzania in the first two years of the COVID-19 pandemic: A cross sectional descriptive study.

[This corrects the article DOI: 10.1371/journal.pgph.0000781.].

Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors.

Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

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: NCT02735707.

Determinants of Implementation of a Critical Care Registry in Asia: Lessons From a Qualitative Study.

BACKGROUND: The Collaboration for Research, Implementation, and Training in Critical Care in Asia (CCA) is implementing a critical care registry to capture real-time data to facilitate service evaluation, quality improvement, and clinical studies. OBJECTIVE: The purpose of this study is to examine stakeholder perspectives on the determinants of implementation of the registry by examining the processes of diffusion, dissemination, and sustainability. METHODS: This study is a qualitative phenomenological inquiry using semistructured interviews with stakeholders involved in registry design, implementation, and use in 4 South Asian countries. The conceptual model of diffusion, dissemination, and sustainability of innovations in health service delivery guided interviews and analysis. Interviews were coded using the Rapid Identification of Themes from Audio recordings procedure and were analyzed based on the constant comparison approach. RESULTS: A total of 32 stakeholders were interviewed. Analysis of stakeholder accounts identified 3 key themes: innovation-system fit; influence of champions; and access to resources and expertise. Determinants of implementation included data sharing, research experience, system resilience, communication and networks, and relative advantage and adaptability. CONCLUSIONS: The implementation of the registry has been possible due to efforts to increase the innovation-system fit, influence of motivated champions, and the support offered by access to resources and expertise. The reliance on individuals and the priorities of other health care actors pose a risk to sustainability.

Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.