Neurological manifestations of COVID-19 in adults and children.

Different neurological manifestations of COVID-19 in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161,239 patients (158,267 adults; 2,972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%), and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%), and central nervous system (CNS) infection (0.2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU vs. non-ICU (7.1% vs. 2.3%, P < .001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease, and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure, and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Evidence of cerebrovascular complications in COVID-19 requiring venovenous extracorporeal membrane oxygenation (ECMO) is limited. Our study aims to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on venovenous ECMO. DESIGN: We analyzed prospectively collected observational data, using univariable and multivariable survival modeling to identify risk factors for stroke. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. SETTING: Three hundred eighty institutions in 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. PATIENTS: Adult COVID-19 patients who were supported by venovenous ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five hundred ninety-five patients (median age [interquartile range], 51 yr [42-59 yr]; male: 70.8%) had venovenous ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity (adjusted hazard ratio [aHR], 2.19; 95% CI, 1.05-4.59) and use of vasopressors before ECMO (aHR, 2.37; 95% CI, 1.08-5.22) were associated with an increased risk of stroke. Forty-eight-hour post-ECMO Paco2-pre-ECMO Paco2/pre-ECMO Paco2 (relative ΔPaco2) of negative 26% and 48-hour post-ECMO Pao2-pre-ECMO Pao2/pre-ECMO Pao2 (relative ΔPao2) of positive 24% at 48 hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPaco2 of negative 17% and relative ΔPao2 of positive 7% in the nonstroke group. Patients with acute stroke had a 79% in-hospital mortality compared with 45% mortality for stroke-free patients. CONCLUSIONS: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on venovenous ECMO. Also, the importance of relative decrease in Paco2 and moderate hyperoxia within 48 hours after ECMO initiation were additional risk factors.

Iliopsoas haematoma during extracorporeal membrane oxygenation: A registry report from the COVID-19 critical care consortium across 30 countries.

INTRODUCTION: Iliopsoas haematoma (IPH) during extracorporeal membrane oxygenation (ECMO) is a rare bleeding complication that can be fatal due to its progression to abdominal compartment syndrome, but its incidence and risk factors are not well known. We have previously reported an IPH incidence rate of 16% in Japan. Among possible reasons for this high incidence, ethnicity has been hypothesised to play a role. Therefore, we used an international multi-centre cohort registry to test this hypothesis by determining the incidence rate of IPH. METHODS: This study was performed using the COVID-19 Critical Care Consortium database, conducted in 30 countries across five continents between 3 January 2020, and 20 June 2022. RESULTS: Overall, 1102 patients received ECMO for COVID-19-related acute respiratory distress syndrome. Of them, only seven were reported to have IPH, indicating an incidence rate of 0.64%, with comparable rates between the countries. The IPH group tended to have a higher mortality rate (71.4%) than the non-IPH group (51%). CONCLUSIONS: Overall incidence of IPH in the studied COVID-19 ECMO cohort was 0.64%. Most cases were reported from Japan, Belgium, and Italy. In our study, this rare complication did not appear to be confined to Asian patients. Due to the high fatality rate, awareness about the occurrence of IPH should be recognised.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.

Creating Accessible Digital Images for Vision Impaired Audiences and Researchers

In 1992, the UN has designated December 3rd each year as the International Day of Persons with Disabilities, an effort that aims to promote the rights and well-being of people with disabilities in all aspects of life. Under the UN Convention of the Rights of Persons with Disabilities, the rights and wellbeing of people with disabilities should be universally accepted and protected. While a laudable goal, thirty years later, we find that these protections are not being met in the museum sector or in the scholarly journals that focus on that work. Curator: The Museum Journal has acknowledged our failure to live up to the spirit of accessibility and continues to work to rectify these deficits in the coming year.Discussion of image accessibility is common in the discourses around social media, and the fields of Computer Science and Human-Computer Interaction, the same cannot be said for the cultural sector. The UK ‘Heritage Access' report (VocalEyes, 2022) demonstrated that digital access to cultural institutions for vision impaired, D/deaf, and neurodivergent users remains very low. They find that information continues to be communicated in ways that are inaccessible, despite the rapidly increasing digital presence of cultural institutions that emerged during the Covid-19 pandemic outbreak. Similarly, the ‘State of accessible publishing in the UK' report (PAAG, 2022) revealed that only a small minority of publishing institutions implemented and integrated accessibility into their workflow and their organizations.

Morbid obesity's impact on COVID-19 patients requiring venovenous extracorporeal membrane oxygenation: The covid-19 critical care consortium database review.

Introduction: Obesity is associated with a worse prognosis in COVID-19 patients with acute respiratory distress syndrome (ARDS). Veno-venous (V-V) Extracorporeal Membrane Oxygenation (ECMO) can be a rescue option, however, the direct impact of morbid obesity in this select group of patients remains unclear.Methods: This is an observational study of critically ill adults with COVID-19 and ARDS supported by V-V ECMO. Data are from 82 institutions participating in the COVID-19 Critical Care Consortium international registry. Patients were admitted between 12 January 2020 to 27 April 2021. They were stratified based on Body Mass Index (BMI) at 40 kg/m2. The endpoint was survival to hospital discharge.Results: Complete data available on 354 of 401 patients supported on V-V ECMO. The characteristics of the high BMI (>40 kg/m2) and lower BMI (≤40 kg/m2) groups were statistically similar. However, the 'high BMI' group were comparatively younger and had a lower APACHE II score. Using survival analysis, older age (Hazard Ratio, HR 1.49 per-10-years, CI 1.25-1.79) and higher BMI (HR 1.15 per-5 kg/m2 increase, CI 1.03-1.28) were associated with a decreased patient survival. A safe BMI threshold above which V-V ECMO would be prohibitive was not apparent and instead, the risk of an adverse outcome increased linearly with BMI.Conclusion: In COVID-19 patients with severe ARDS who require V-V ECMO, there is an increased risk of death associated with age and BMI. The risk is linear and there is no BMI threshold beyond which the risk for death greatly increases.

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies.

BACKGROUND: Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic. METHODS: The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort. RESULTS: Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population. CONCLUSION: AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.

The Use of Noninvasive Multimodal Neuromonitoring in Adult Critically Ill Patients With COVID-19 Infection.

INTRODUCTION: Noninvasive neuromonitoring could be a valuable option for bedside assessment of cerebral dysfunction in patients with coronavirus disease-2019 (COVID-19) admitted to intensive care units (ICUs). This systematic review aims to investigate the use of noninvasive multimodal neuromonitoring in critically ill adult patients with COVID-19 infection. METHODS: MEDLINE/PubMed, Scopus, Cochrane, and EMBASE databases were searched for studies investigating noninvasive neuromonitoring in patients with COVID-19 admitted to ICUs. The monitoring included transcranial Doppler ultrasonography (TCD), the Brain4care Corp. cerebral compliance monitor (B4C), optic nerve sheath diameter (ONSD), near infrared spectroscopy, automated pupillometry, and electroencephalography (EEG). RESULTS: Thirty-two studies that investigated noninvasive neuromonitoring techniques in patients with COVID-19 in the ICU were identified from a systematic search of 7001 articles: 1 study investigating TCD, ONSD and pupillometry; 2 studies investigating the B4C device and TCD; 3 studies investigating near infrared spectroscopy and TCD; 4 studies investigating TCD; 1 case series investigating pupillometry, and 21 studies investigating EEG. One hundred and nineteen patients underwent TCD monitoring, 47 pupillometry, 49 ONSD assessment, 50 compliance monitoring with the B4C device, and 900 EEG monitoring. Alterations in cerebral hemodynamics, brain compliance, brain oxygenation, pupillary response, and brain electrophysiological activity were common in patients with COVID-19 admitted to the ICU; these abnormalities were not clearly associated with worse outcome or the development of new neurological complications. CONCLUSIONS: The use of noninvasive multimodal neuromonitoring in critically ill COVID-19 patients could be considered to facilitate the detection of neurological derangements. Determining whether such findings allow earlier detection of neurological complications or guide appropriate therapy requires additional studies.

Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study.

Introduction: Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods: This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination: The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number: ACTRN12620000421932.

Tracheostomy outcomes in critically ill patients with COVID-19: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: We performed a systematic review of mechanically ventilated patients with COVID-19, which analysed the effect of tracheostomy timing and technique (surgical vs percutaneous) on mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS), decannulation from tracheostomy, duration of mechanical ventilation, and complications. METHODS: Four databases were screened between January 1, 2020 and January 10, 2022 (PubMed, Embase, Scopus, and Cochrane). Papers were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population or Problem, Intervention or exposure, Comparison, and Outcome (PICO) guidelines. Meta-analysis and meta-regression for main outcomes were performed. RESULTS: The search yielded 9024 potentially relevant studies, of which 47 (n=5268 patients) were included. High levels of between-study heterogeneity were observed across study outcomes. The pooled mean tracheostomy timing was 16.5 days (95% confidence interval [CI]: 14.7-18.4; I2=99.6%). Pooled mortality was 22.1% (95% CI: 18.7-25.5; I2=89.0%). Meta-regression did not show significant associations between mortality and tracheostomy timing, mechanical ventilation duration, time to decannulation, and tracheostomy technique. Pooled mean estimates for ICU and hospital LOS were 29.6 (95% CI: 24.0-35.2; I2=98.6%) and 38.8 (95% CI: 32.1-45.6; I2=95.7%) days, both associated with mechanical ventilation duration (coefficient 0.8 [95% CI: 0.2-1.4], P=0.02 and 0.9 [95% CI: 0.4-1.4], P=0.01, respectively) but not tracheostomy timing. Data were insufficient to assess tracheostomy technique on LOS. Duration of mechanical ventilation was 23.4 days (95% CI: 19.2-27.7; I2=99.3%), not associated with tracheostomy timing. Data were insufficient to assess the effect of tracheostomy technique on mechanical ventilation duration. Time to decannulation was 23.8 days (95% CI: 19.7-27.8; I2=98.7%), not influenced by tracheostomy timing or technique. The most common complications were stoma infection, ulcers or necrosis, and bleeding. CONCLUSIONS: In patients with COVID-19 requiring tracheostomy, the timing and technique of tracheostomy did not clearly impact on patient outcomes. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021272220.

Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study.

OBJECTIVE: To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. DESIGN: Observational study. SETTING: 30 countries across five continents, 3 January 2020 to 29 August 2021. PARTICIPANTS: 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. INTERVENTIONS: ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. MAIN OUTCOME MEASURE: The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. RESULTS: 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO2/FiO2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference -7.1%, 95% confidence interval -8.2% to -6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO2/FiO2 <80 mm Hg or with driving pressures >15 cmH2O during the first 10 days of mechanical ventilation. CONCLUSIONS: ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

ECMO simulation training during a worldwide pandemic: The role of ECMO telesimulation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy used in the most severe forms of acute respiratory distress syndrome. Due to its intrinsic complexity and relatively low annual volume, simulation is essential for efficient and appropriate ECMO management. COVID-19 has limited the opportunities for high-fidelity in-person simulation training when many hospitals are looking to expand their ECMO services to battle the ongoing pandemic. To meet this demand, the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia, conducted a 3-day ECMO course entailing online didactic lectures (adult and paediatric stream), water drills and telesimulation. PURPOSE: The purpose of the study is to report the evaluation result of this novel model of education during COVID-19 outbreak. DATA COLLECTION: Participants were given an ECMO knowledge pre-course and post-course test and a telesimulation evaluation survey at the conclusion and these data were collected. RESULTS: The course was attended by 104 physicians, critical care nurses and perfusionists. Pre-course and post-course assessments showed a significant improvement in ECMO knowledge (60.0% vs 73.3%, respectively). Overall, the participants rated the telesimulation positively, and most found it acceptable to in-person simulation training considering the pandemic restrictions. CONCLUSION: Despite the complexities of ECMO, our recent experience demonstrates ECMO education and simulation delivered online is feasible, welcomed and supportive of a change in ECMO training course format. As we incorporate more innovative digital technologies, telesimulation may further enhance the quality of future ECMO training.

Non-Invasive Multimodal Neuromonitoring in Non-Critically Ill Hospitalized Adult Patients With COVID-19: A Systematic Review and Meta-Analysis.

Introduction: Neurological complications are frequent in patients with coronavirus disease-2019 (COVID-19). The use of non-invasive neuromonitoring in subjects without primary brain injury but with potential neurological derangement is gaining attention outside the intensive care unit (ICU). This systematic review and meta-analysis investigates the use of non-invasive multimodal neuromonitoring of the brain in non-critically ill patients with COVID-19 outside the ICU and quantifies the prevalence of abnormal neuromonitoring findings in this population. Methods: A structured literature search was performed in MEDLINE/PubMed, Scopus, Cochrane, and EMBASE to investigate the use of non-invasive neuromonitoring tools, including transcranial doppler (TCD); optic nerve sheath diameter (ONSD); near-infrared spectroscopy (NIRS); pupillometry; and electroencephalography (EEG) inpatients with COVID-19 outside the ICU. The proportion of non-ICU patients with CVOID-19 and a particular neurological feature at neuromonitoring at the study time was defined as prevalence. Results: A total of 6,593 records were identified through literature searching. Twenty-one studies were finally selected, comprising 368 non-ICU patients, of whom 97 were considered for the prevalence of meta-analysis. The pooled prevalence of electroencephalographic seizures, periodic and rhythmic patterns, slow background abnormalities, and abnormal background on EEG was.17 (95% CI 0.04-0.29), 0.42 (95% CI 0.01-0.82), 0.92 (95% CI 0.83-1.01), and.95 (95% CI 0.088-1.09), respectively. No studies investigating NIRS and ONSD outside the ICU were found. The pooled prevalence for abnormal neuromonitoring findings detected using the TCD and pupillometry were incomputable due to insufficient data. Conclusions: Neuromonitoring tools are non-invasive, less expensive, safe, and bedside available tools with a great potential for both diagnosis and monitoring of patients with COVID-19 at risk of brain derangements. However, extensive literature searching reveals that they are rarely used outside critical care settings.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=265617, identifier: CRD42021265617.

Evaluation of an emergency safe supply drugs and managed alcohol program in COVID-19 isolation hotel shelters for people experiencing homelessness.

BACKGROUND: During a COVID-19 outbreak in the congregate shelter system in Halifax, Nova Scotia, Canada, a healthcare team provided an emergency "safe supply" of medications and alcohol to facilitate isolation in COVID-19 hotel shelters for residents who use drugs and/or alcohol. We aimed to evaluate (a) substances and dosages provided, and (b) outcomes of the program. METHODS: We reviewed medical records of all COVID-19 isolation hotel shelter residents during May 2021. The primary outcome was successful completion of 14 days isolation, as directed by public health orders. Adverse events included (a) overdose; (b) intoxication; and (c) diversion, selling, or sharing of medications or alcohol. RESULTS: Seventy-seven isolation hotel residents were assessed (mean age 42 ± 14 years; 24% women). Sixty-two (81%) residents were provided medications, alcohol, or cigarettes. Seventeen residents (22%) received opioid agonist treatment (methadone, buprenorphine, or slow-release oral morphine) and 27 (35%) received hydromorphone. Thirty-one (40%) residents received prescriptions stimulants. Six (8%) residents received benzodiazepines and forty-two (55%) received alcohol. Over 14 days, mean daily dosages increased of hydromorphone (45 ± 32 - 57 ± 42 mg), methylphenidate (51 ± 28 - 77 ± 37 mg), and alcohol (12.3 ± 7.6 - 13.0 ± 6.9 standard drinks). Six residents (8%) left isolation prematurely, but four returned. During 1059 person-days, there were zero overdoses. Documented concerns regarding intoxication occurred six times (0.005 events/person-day) and medication diversion/sharing three times (0.003 events/person-day). CONCLUSIONS: COVID-19 isolation hotel residents participating in an emergency safe supply and managed alcohol program experienced high rates of successful completion of 14 days isolation and low rates of adverse events.

Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study.

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .