Long-term Safety of Directly Discharging Patients Home from the ICU Compared to Ward Transfer.

Purpose: To evaluate the long-term safety of directly discharging intensive care unit (ICU) survivors to their home. Methods: A retrospective observational cohort of 341 ICU survivors who were directly discharged home from the ICU ("direct discharge") or discharged home ≤72 hours after ICU transfer to the ward ("ward transfer") was conducted in Regina, Saskatchewan ICUs between September 1, 2016 and September 30, 2018. The primary outcome was 90-day hospital readmission. Secondary outcomes included 30-day, 90-day, and 365-day emergency department (ED) visits, 30-day and 365-day hospital readmissions, and 365-day mortality. All outcomes were evaluated by multivariable Cox regression after adjustment for demographic and clinical characteristics. Results: Of 341 survivors (25.5% of total ICU visits), 148 (43.4%) patients were direct discharges and 193 (56.6%) were ward transfers. The median age was 46 years (interquartile range, 34-62), 38.4% were female, and 61.8% resided in Regina. Compared to the ward transfer cohort, more patients in the direct discharge cohort had at least one 90-day hospital readmission (30.4% versus 17.1% of patients, adjusted hazard ratio 2.09, 95% confidence interval 1.28-3.40, P = .003), after adjustment. Additionally, there were more 90-day ED visits (P = .045), and 30-day (P = .049) and 365-day hospital readmissions (P = .03), after adjustment. Conclusions: In Saskatchewan, direct discharge compared to ward transfer was associated with an increase in 90-day hospital readmissions, and potentially other clinical outcomes. Further study is necessary.

Hospital admissions and mortality due to complications of injection drug use in two hospitals in Regina, Canada: retrospective chart review.

BACKGROUND: Infectious complications of injection drug use (IDU) often require lengthy inpatient treatment. Our objective was to identify the number of admissions related to IDU in Regina, Canada, as well as describe patient demographics and comorbidities, yearly mortality, readmission rate, and cumulative cost of these hospitalizations between January 1 and December 31, 2018. Additionally, we sought to identify factors that increased risk of death or readmission. METHODS: This study is a retrospective chart review conducted at the two hospitals in Regina. Eligible study cases were identified by querying the discharge database for predetermined International Classification of Diseases code combinations. Electronic medical records were reviewed to assess whether each admission met inclusion criteria, and hospitalization and patient data were subsequently extracted for all included admissions. Mortality data were gleaned from hospital and Ministry of Health databases. Data were analyzed using Excel and IBM SPSS Statistics to identify common comorbidities, admission diagnoses, and costs, as well as to compare patients with a single admission during the study period to those with multiple admissions. Logistic regression analysis was used to identify the relationship between individual variables and in- and out-of-hospital annual mortality. RESULTS: One hundred and forty-nine admissions were included, with 102 unique patients identified. Common comorbidities included hepatitis C (47%), human immunodeficiency virus (HIV) (25%), and comorbid psychiatric disorders (19%). In 23% of all admissions, patients left hospital prior to treatment completion, and 27% of patients experienced multiple admissions. Female patients and those with chronic pain were more likely to be readmitted (p = 0.024 and p = 0.029, respectively). Patients admitted with infective endocarditis were more likely to die during hospitalization (p = 0.0001). The overall mortality was 15% in our cohort. The estimated cumulative cost of inpatient treatment of complications of IDU in Regina was $3.7 million CAD in 2018. CONCLUSION: Patients with history of IDU and hospital admission experience high mortality rates in Regina, a city with paucity of inpatient supports for persons who use injection drugs. Needle syringe programs, opioid agonist therapy, and safe consumption sites have been shown to improve outcomes as well as reduce healthcare costs for this patient population. We will use our findings to advocate for increased access to these harm reduction strategies in Regina, particularly for inpatients.

Evaluating service needs for veno-venous extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome in Saskatchewan.

To determine the number of patients with acute respiratory distress syndrome (ARDS) who would be eligible to receive veno-venous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective observational study of ARDS patients admitted to Regina General Hospital Intensive Care Unit (ICU). VV-ECMO eligibility was assessed using selection criteria from the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Syndrome trial (EOLIA), the Extracorporeal Life Support Organization (ELSO), New South Wales (NSW), Critical Care Services Ontario (CCSO) and a Regina-restrictive criteria. Of 415 patients admitted between October 16, 2018, and January 21, 2021, 103 (25%) had mild, 175 (42%) had moderate, and 64 (15%) had severe ARDS. Of the cohort, 144 (35%) had bacterial pneumonia, 86 (21%) had viral pneumonia (including COVID-19), and 72 (17%) had aspiration pneumonia. Using the EOLIA, ELSO, NSW, CCSO and Regina-restrictive criteria, 7/415 (1.7%), 6/415 (1.5%), 19/415 (4.6%), 26/415 (6.3%) and 12/415 (2.9%) were eligible for VV-ECMO, respectively. Of all ECMO-eligible patients, only one (2.4%) actually received VV-ECMO, 20/42 (48%) received prone positioning and 21/42 (50%) received neuromuscular blockade. There is potential for service expansion of VV-ECMO in Regina; however, there is still a need to improve the delivery of evidence-based ARDS therapies.

Treatments and Outcomes of Critically Ill Patients with Candida spp. Colonization of the Lower Respiratory Tract in Regina, Saskatchewan.

Background: Among critically ill patients receiving mechanical ventilation, Candida spp. are commonly detected in the lower respiratory tract (LRT). This is generally considered to represent colonization. Objective: To evaluate the use of antifungal treatments and the clinical outcomes of patients with Candida colonization of the LRT. Methods: This retrospective analysis involved consecutive patients admitted to the intensive care unit between April 2016 and May 2021with positive results on Candida spp. testing of LRT samples. Data related to antifungal treatment and clinical outcomes were analyzed descriptively, and multivariable logistic regression was performed. Results: Of 200 patients initially identified, 160 (80%) died in hospital. Antifungal therapy was given to 103 (51.5%) of the patients, with treatment being more likely among those with shock and those who received parenteral nutrition. Mortality was high among patients with positive Candida results on LRT culture, regardless of treatment. Multivariable logistic regression, with adjustment for age, sex, comorbidities, and sequential organ failure assessment (SOFA) score, showed that antifungal treatment was associated with lower odds of death (odds ratio 0.39, 95% confidence interval 0.17-0.87) compared with no treatment (p = 0.021). Conclusions: This study showed higher mortality rates than have been reported previously. Further investigation into the role of antifungal therapy among critically ill patients with Candida spp. colonization is required.

Contexte: Chez les patients gravement malades recevant une ventilation mécanique, les Candida spp. sont fréquemment détectées dans les voies respiratoires inférieures (VRI) ­ une situation généralement considérée comme une colonisation. Objectif: Évaluer l'utilisation d'un traitement antifongique et les résultats cliniques chez les patients présentant une colonisation par Candida dans les VRI. Méthodes: Cette analyse rétrospective portait sur des patients consécutifs de l'unité de soins intensifs ayant obtenu un résultat positif au test de Candida sur les isolats des VRI entre avril 2016 et mai 2021. Les données relatives au traitement antifongique et aux résultats cliniques ont été analysées de manière descriptive, et une régression logistique multivariable a été effectuée. Résultats: Parmi les 200 patients initialement recensés, 160 (80 %) sont décédés à l'hôpital. Une thérapie antifongique a été administrée à 103 (51,5 %) des patients, et le traitement était plus probable chez ceux en état de choc et ceux ayant reçu une nutrition parentérale. Les patients ayant été déclarés positifs pour la Candida dans la culture des VRI présentaient un taux de mortalité élevé, indépendamment du traitement. Une régression logistique multivariable, avec ajustement pour l'âge, le sexe, les comorbidités et le score SOFA (sequential organ failure assessment), a montré que le traitement antifongique était associé à une probabilité de décès réduite (rapport de cotes 0,39; intervalle de confiance à 95 % 0,17­0,87), par rapport à l'absence de traitement (p = 0,021). Conclusions: Cette étude a révélé des taux de mortalité plus élevés que ce qui avait été rapporté précédemment. Une enquête plus approfondie sur le rôle de la thérapie antifongique chez les patients gravement malades présentant une colonisation par Candida spp. est nécessaire.

External validation of the hospital frailty risk score among older adults receiving mechanical ventilation.

To externally validate the Hospital Frailty Risk Score (HFRS) in critically ill patients. We selected older adult (≥ 75 years old) hospitalizations receiving mechanical ventilation, using the Nationwide Readmissions Database (January 1, 2016-November 30, 2018). Frailty risk was subcategorized into low-risk (HFRS score < 5), intermediate-risk (score 5-15), and high-risk (score > 15). We evaluated the HFRS to predict in-hospital mortality, prolonged hospitalization, and 30-day readmissions, using multivariable logistic regression, adjusting for patient and hospital characteristics. Model performance was assessed using the c-statistic, Brier score, and calibration plots. Among 649,330 weighted hospitalizations, 9.5%, 68.3%, and 22.2% were subcategorized as low-, intermediate-, and high-risk for frailty, respectively. After adjustment, high-risk patient hospitalizations were associated with increased risks of prolonged hospitalization (adjusted odds ratio [aOR] 5.59 [95% confidence interval [CI] 5.24-5.97], c-statistic 0.694, Brier 0.216) and 30-day readmissions (aOR 1.20 [95% CI 1.13-1.27], c-statistic 0.595, Brier 0.162), compared to low-risk hospitalizations. Conversely, high-risk hospitalizations were inversely associated with in-hospital mortality (aOR 0.46 [95% CI 0.45-0.48], c-statistic 0.712, Brier 0.214). The HFRS was not successfully validated to predict in-hospital mortality in critically ill older adults. While it may predict other outcomes, its use should be avoided in the critically ill.

A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals New Mechanisms of Redox Homeostasis and NF-κB Signaling.

Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs); however, the discovery of the molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using mass spectrometry (MS)-based analysis of 210 affinity-purified mitochondrial (mt) fractions isolated from 27 epitope-tagged human ND-linked MPs in HEK293 cells, we report a high-confidence MP network including 1,964 interactions among 772 proteins (>90% previously unreported). Nearly three-fourths of these interactions were confirmed in mouse brain and multiple human differentiated neuronal cell lines by primary antibody immunoprecipitation and MS, with many linked to NDs and autism. We show that the SOD1-PRDX5 interaction, critical for mt redox homeostasis, can be perturbed by amyotrophic lateral sclerosis-linked SOD1 allelic variants and establish a functional role for ND-linked factors coupled with IκBɛ in NF-κB activation. Our results identify mechanisms for ND-linked MPs and expand the human mt interaction landscape.

Exploring mitochondrial system properties of neurodegenerative diseases through interactome mapping.

Mitochondria are double membraned, dynamic organelles that are required for a large number of cellular processes, and defects in their function have emerged as causative factors for a growing number of human disorders and are highly associated with cancer, metabolic, and neurodegenerative (ND) diseases. Biochemical and genetic investigations have uncovered small numbers of candidate mitochondrial proteins (MPs) involved in ND disease, but given the diversity of processes affected by MP function and the difficulty of detecting interactions involving these proteins, many more likely remain unknown. However, high-throughput proteomic and genomic approaches developed in genetically tractable model prokaryotes and lower eukaryotes have proven to be effective tools for querying the physical (protein-protein) and functional (gene-gene) relationships between diverse types of proteins, including cytosolic and membrane proteins. In this review, we highlight how experimental and computational approaches developed recently by our group and others can be effectively used towards elucidating the mitochondrial interactome in an unbiased and systematic manner to uncover network-based connections. We discuss how the knowledge from the resulting interaction networks can effectively contribute towards the identification of new mitochondrial disease gene candidates, and thus further clarify the role of mitochondrial biology and the complex etiologies of ND disease. BIOLOGICAL SIGNIFICANCE: Biochemical and genetic investigations have uncovered small numbers of candidate mitochondrial proteins (MPs) involved in neurodegenerative (ND) diseases, but given the diversity of processes affected by MP function and the difficulty of detecting interactions involving these proteins, many more likely remain unknown. Large-scale proteomic and genomic approaches developed in model prokaryotes and lower eukaryotes have proven to be effective tools for querying the physical (protein-protein) and functional (gene-gene) relationships between diverse types of proteins. Extension of this new framework to the mitochondrial sub-system in human will likewise provide a universally informative systems-level view of the physical and functional landscape for exploring the evolutionary principles underlying mitochondrial function. In this review, we highlight how experimental and computational approaches developed recently by our group and others can be effectively used towards elucidating the mitochondrial interactome in an unbiased and systematic manner to uncover network-based connections. We anticipate that the knowledge from these resulting interaction networks can effectively contribute towards the identification of new mitochondrial disease gene candidates, and thus foster a deeper molecular understanding of mitochondrial biology as well as the etiology of mitochondrial diseases. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes?