An Agent-Based Modeling and Virtual Reality Application Using Distributed Simulation: Case of a COVID-19 Intensive Care Unit.

Hospitals and other healthcare settings use various simulation methods to improve their operations, management, and training. The COVID-19 pandemic, with the resulting necessity for rapid and remote assessment, has highlighted the critical role of modeling and simulation in healthcare, particularly distributed simulation (DS). DS enables integration of heterogeneous simulations to further increase the usability and effectiveness of individual simulations. This article presents a DS system that integrates two different simulations developed for a hospital intensive care unit (ICU) ward dedicated to COVID-19 patients. AnyLogic has been used to develop a simulation model of the ICU ward using agent-based and discrete event modeling methods. This simulation depicts and measures physical contacts between healthcare providers and patients. The Unity platform has been utilized to develop a virtual reality simulation of the ICU environment and operations. The high-level architecture, an IEEE standard for DS, has been used to build a cloud-based DS system by integrating and synchronizing the two simulation platforms. While enhancing the capabilities of both simulations, the DS system can be used for training purposes and assessment of different managerial and operational decisions to minimize contacts and disease transmission in the ICU ward by enabling data exchange between the two simulations.

A Case of Fat Embolism Syndrome with Cerebral Involvement in Sickle Cell Anemia.

Fat embolism syndrome (FES) is a rare condition that can occur as a complication of sickle cell disease. We describe a case of a patient with sickle cell disease (homozygous Hb S or HBB: c.20A>T) presenting with initial signs and symptoms consistent with a vaso-occlusive crisis (VOC). Within 24 hours, the patient developed evidence of coagulopathy, multi organ failure and a reduced level of consciousness (LOC) prompting intubation. A diagnosis of FES was made on the basis of the patient's clinical presentation, in conjunction with magnetic resonance imaging (MRI) of the brain revealing innumerable tiny foci of restricted diffusion, intracytoplasmic microvesicular fat on Sudan Red staining of bronchoalveolar lavage samples and evidence of a pulmonary shunt on echocardiogram bubble study. Red blood cell (RBC) exchange transfusion was initiated 3 days following initial presentation and no further exchange transfusions were needed on the basis of subsequent Hb S (HBB: c.20A>T) levels. The LOC gradually improved and the patient was extubated 12 days following presentation. Neurological improvement was slow, with mild cognitive impairment initially evident at 3 months and no cognitive or neurological deficits remaining within 6 months of admission. This case highlights the importance of understanding the pathophysiology and clinical presentation of FES, as early exchange transfusion may improve survival in patients with sickle cell disease and FES.

α2-6-Neosialidase: A Sialyltransferase Mutant as a Sialyl Linkage-Specific Sialidase.

The lack of α2-6-linkage specific sialidases limits the structural and functional studies of sialic-acid-containing molecules. Photobacterium damselae α2-6-sialyltransferase (Pd2,6ST) was shown previously to have α2-6-specific, but weak, sialidase activity. Here, we develop a high-throughput blue-white colony screening method to identify Pd2,6ST mutants with improved α2-6-sialidase activity from mutant libraries generated by sequential saturation mutagenesis. A triple mutant (Pd2,6ST S232L/T356S/W361F) has been identified with 100-fold improved activity, high α2-6-sialyl linkage selectivity, and ability to cleave two common sialic acid forms, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). It is a valuable tool for sialoglycan structural analysis and functional characterization. The sequential saturation mutagenesis and screening strategy developed here can be explored to evolve other linkage-specific neoglycosidases from the corresponding glycosyltransferases.

One-Year Outcomes in Caregivers of Critically Ill Patients.

BACKGROUND: Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). METHODS: We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. RESULTS: The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. CONCLUSIONS: In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).

The RECOVER Program: Disability Risk Groups and 1-Year Outcome after 7 or More Days of Mechanical Ventilation.

RATIONALE: Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design. OBJECTIVES: To stratify patients for post-ICU disability and recovery to 1 year after critical illness. METHODS: We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling. MEASUREMENTS AND MAIN RESULTS: The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year. CONCLUSIONS: ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

Early sedation use in critically ill mechanically ventilated patients: when less is really more.

Over the last 10 years, there has been an explosion of literature surrounding sedation management for critically ill patients. The clinical target has moved away from an unconscious and immobile patient toward a goal of light or no sedation and early mobility. The move away from terms such as 'sedation' toward more patient-centered and symptom-based control of pain, anxiety, and agitation makes the management of critically ill patients more individualized and dynamic. Over-sedation has been associated with negative ICU outcomes, including longer durations of mechanical ventilation and lengths of stay, but few studies have been able to associate deep sedation with increased mortality.

ICU-acquired weakness: what is preventing its rehabilitation in critically ill patients?

Intensive care unit-acquired weakness (ICUAW) has been recognized as an important and persistent complication in survivors of critical illness. The absence of a consistent nomenclature and diagnostic criteria for ICUAW has made research in this area challenging. Although many risk factors have been identified, the data supporting their direct association have been controversial. Presently, there is a growing body of literature supporting the utility and benefit of early mobility in reducing the morbidity from ICUAW, but few centers have adopted this into their ICU procedures. Ultimately, the implementation of such a strategy would require a shift in the knowledge and culture within the ICU, and may be facilitated by novel technology and patient care strategies. The purpose of this article is to briefly review the diagnosis, risk factors, and management of ICUAW, and to discuss some of the barriers and novel treatments to improve outcomes for our ICU survivors.

Education and support needs during recovery in acute respiratory distress syndrome survivors.

INTRODUCTION: There is a limited understanding of the long-term needs of survivors of the acute respiratory distress syndrome (ARDS) as they recover from their episode of critical illness. The Timing it Right (TIR) framework, which emphasizes ARDS survivors' journey from the ICU through to community re-integration, may provide a valuable construct to explore the support needs of ARDS survivors during their recovery. METHODS: Twenty-five ARDS survivors participated in qualitative interviews examining their needs for educational, emotional and tangible support for each phase of the TIR framework. Transcripts were analyzed using framework methodology. RESULTS: ARDS survivors' support needs varied across the illness trajectory. During the ICU stay, survivors were generally too ill to require information. The transfer to the general ward was characterized by anxiety surrounding decreased surveillance and concern for future health and treatment. Information needs focused on the events surrounding the acute illness, while physical and emotional needs revolved around physical therapy and psychological support for depression and anxiety. As patients were preparing for hospital discharge, they expressed a desire for specific information about the recovery and rehabilitation process following an episode of ARDS (e.g., outpatient physiotherapy, long-term sequela of the illness). Once in the community, survivors wanted guidance on home care, secondary prevention, and ARDS support groups. CONCLUSIONS: Our findings support the need for future educational and support interventions to meet the changing needs of ARDS survivors during their recovery.

Chronic sleep disorders in survivors of the acute respiratory distress syndrome.

PURPOSE: Sleep disruption is well recognized in the Intensive Care Unit. Poor sleep quality likely continues following discharge from hospital in several patients and becomes a chronic disorder in some. The aim of this study was to describe the etiology of chronic sleep complaints in survivors of ARDS. METHODS: Seven ARDS survivors with no previous sleep complaints who reported difficulty sleeping 6 months or more following discharge from hospital were evaluated. Sleep quality was assessed subjectively with a sleep history and the Insomnia Severity Index and objectively with polysomnography. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. RESULTS: A chronic sleep disorder was identified in each patient who reported difficulty sleeping. The primary sleep disorder was chronic conditioned insomnia (5 patients), parasomnia (1 patient) and obstructive sleep apnea (1 patient). In addition, 4 patients had periodic leg movements, which was of uncertain clinical significance. CONCLUSION: Chronic sleep disorders, which originate during the acute illness, are present in some ARDS survivors several months after discharge from hospital. If unrecognized, lack of treatment may contribute to impaired quality of life and incomplete rehabilitation from their critical illness.