ORCID Profile
0000-0002-5799-3619
Current Organisation
The University of Manitoba
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Publisher: Springer International Publishing
Date: 2022
Publisher: Frontiers Media SA
Date: 12-08-2021
DOI: 10.3389/FNEUR.2021.664599
Abstract: Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke ( n = 226), delirium ( n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis ( n = 13), seizures ( n = 3), and acute demyelinating encephalitis ( n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome ( n = 21) and other peripheral neuropathies ( n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9–1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0–4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0–0.8%, 6/1,006]. Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of in iduals at higher risk for neurologic sequelae.
Publisher: SAGE Publications
Date: 08-02-2023
DOI: 10.1177/02676591231156487
Abstract: 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/m 2 . 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 ( kg/m 2 ) and lower BMI (≤40 kg/m 2 ) 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/m 2 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.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2022
DOI: 10.1186/S13054-022-03983-5
Abstract: 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. We analyzed a convenience s le 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. 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). 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.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Wiley
Date: 27-09-2023
DOI: 10.1111/IMM.13577
Abstract: 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 s les, 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.
Publisher: Frontiers Media SA
Date: 22-07-2022
Abstract: 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. 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. 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. ACTRN12620000421932.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-07-2021
DOI: 10.1097/CCM.0000000000005209
Abstract: Stroke has been reported in observational series as a frequent complication of coronavirus disease 2019, but more information is needed regarding stroke prevalence and outcomes. We explored the prevalence and outcomes of acute stroke in an international cohort of patients with coronavirus disease 2019 who required ICU admission. Retrospective analysis of prospectively collected database. A registry of coronavirus disease 2019 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with acute stroke during their stay. Patients older than 18 years old with acute coronavirus disease 2019 infection in ICU. None. Of 2,699 patients identified (median age 59 yr male 65%), 59 (2.2%) experienced acute stroke: 0.7% ischemic, 1.0% hemorrhagic, and 0.5% unspecified type. Systemic anticoagulant use was not associated with any stroke type. The frequency of diabetes, hypertension, and smoking was higher in patients with ischemic stroke than in stroke-free and hemorrhagic stroke patients. Extracorporeal membrane oxygenation support was more common among patients with hemorrhagic (56%) and ischemic stroke (16%) than in those without stroke (10%). Extracorporeal membrane oxygenation patients had higher cumulative 90-day probabilities of hemorrhagic (relative risk = 10.5) and ischemic stroke (relative risk = 1.7) versus nonextracorporeal membrane oxygenation patients. Hemorrhagic stroke increased the hazard of death (hazard ratio = 2.74), but ischemic stroke did not—similar to the effects of these stroke types seen in noncoronavirus disease 2019 ICU patients. In an international registry of ICU patients with coronavirus disease 2019, stroke was infrequent. Hemorrhagic stroke, but not ischemic stroke, was associated with increased mortality. Further, both hemorrhagic stroke and ischemic stroke were associated with traditional vascular risk factors. Extracorporeal membrane oxygenation use was strongly associated with both stroke and death.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2022
DOI: 10.1007/S00134-022-06660-X
Abstract: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2022
DOI: 10.1186/S12872-022-02565-1
Abstract: 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. 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. 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. 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: www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .
Publisher: Springer Science and Business Media LLC
Date: 09-06-2021
DOI: 10.1186/S13054-021-03518-4
Abstract: Heterogeneous respiratory system static compliance ( C RS ) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe C RS —calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of C RS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). C RS , within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV ( p = 0.417) nor with PaO 2 /FiO 2 ( p = 0.100). Females presented lower C RS than males (95% CI of C RS difference between females-males: − 11.8 to − 7.4 mL/cmH 2 O p 0.001), and although females presented higher body mass index (BMI), association of BMI with C RS was marginal ( p = 0.139). Ventilatory management varied across C RS range, resulting in a significant association between C RS and driving pressure (estimated decrease − 0.31 cmH 2 O/L per mL/cmH 2 0 of C RS , 95% CI − 0.48 to − 0.14, p 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that C RS (+ 10 mL/cm H 2 O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018). This multicentre report provides a comprehensive account of C RS in COVID-19 patients on MV. C RS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at tudy . Trial registration : ACTRN12620000421932.
Publisher: Frontiers Media SA
Date: 14-04-2022
DOI: 10.3389/FNEUR.2022.814405
Abstract: 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. 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. 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. 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 rospero/display_record.php?RecordID=265617 , identifier: CRD42021265617.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-02-2023
DOI: 10.1097/CCM.0000000000005798
Abstract: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. Prospective, observational study. Two hundred twenty-nine ICUs across 32 countries. Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. None. 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). 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.
Publisher: Cold Spring Harbor Laboratory
Date: 31-03-2022
DOI: 10.1101/2022.03.24.22272732
Abstract: 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 govern this remain unknown. In this study, we investigated the landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, and 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 s les, were further confirmed by γ−H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of Interferon-stimulated genes (ISGs), 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
DOI: 10.1097/EJA.0000000000001131
Abstract: Delirium is common in the ICU, with incidence rates reported to be upwards of 70%. Due to the significant morbidity and mortality associated with delirium, it is hypothesised that a delirium-free sedative agent will improve outcomes in older adults admitted to the ICU. To assess if dexmedetomidine sedation is associated with a reduction in ICU delirium among older adults, and to evaluate its risks and benefits compared with propofol sedation. Systematic review of randomised controlled trials and cohort studies with meta-analyses. Articles published from database inception to 8 April 2019 were retrieved from Medline, EMBASE, Evidence-based Medicine Reviews, International Pharmaceutical Abstracts, Scopus, ClinicalTrials.gov and WHO Trials. Studies were included if they compared dexmedetomidine sedation with propofol in the ICU, reported the incidence of delirium as an outcome and had a mean/median s le age of at least 60. Studies that examined dexmedetomidine and propofol use intra-operatively or as part of general anaesthesia were excluded. Dexmedetomidine sedation was associated with a lower incidence of delirium when compared with propofol: seven studies, n =1249 risk ratio 0.70 95% confidence interval (CI) 0.52 to 0.95 P = 0.02. There was no statistically significant difference in the incidence of bradycardia: three studies, n =278 risk ratio 1.52 95% CI 0.85 to 2.72 P = 0.16, and hypotension: six studies, n =867 patients risk ratio 1.12 95% CI 0.86 to 1.45 P = 0.42. Dexmedetomidine sedation did not reduce hospital length of stay, ICU length of stay or duration of mechanical ventilation compared with propofol. Compared with propofol, dexmedetomidine sedation in the ICU is associated with lower delirium incidence among older adults with no significant increase in adverse events. In older adult ICU patients at risk of developing delirium, sedation with dexmedetomidine should be considered. Further research is warranted to elucidate and explain the mechanisms underlying this process, and to confirm our findings with large, multicentre trials. The study protocol has been registered in PROSPERO (CRD42018099339).
No related grants have been discovered for Rakesh Arora.