Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

PURPOSE: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research. METHODS: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials. RESULTS: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction). CONCLUSION: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion.

RéSUMé: OBJECTIF: La recherche en soins intensifs au Canada est principalement réalisée dans des unités de soins intensifs affiliées à des centres universitaires jouissant d'infrastructures de recherche bien établies. Des efforts ont été déployés pour engager les unités de soins intensifs des hôpitaux communautaires en recherche, mais les impacts de leur participation à la recherche clinique n'ont jamais été explicitement quantifiés. Nous avons conséquemment cherché à déterminer le nombre de patient·es additionnel·les pouvant être recruté·es dans des études de soins critiques ainsi que la variation du temps nécessaire pour compléter les études si la patientèle issue d'unités de soins intensifs d'hôpitaux communautaires participait à la recherche clinique. MéTHODE: Une analyse par arbre de décision a été réalisée à partir de données provenant des Alberta Health Services pour l'année 2018. Les données démographiques et les caractéristiques cliniques de tou·tes les patient·es admis·es aux soins intensifs ont été comparées avec les critères d'éligibilité de dix importantes études multicentriques, randomisées, contrôlées en soins intensifs. Les patient·es des unités de soins intensifs universitaires et communautaires ont tou·tes été évalué·es pour leur éligibilité à chacune des dix études, et des modèles d'arbres décisionnels ont été construits en se basant sur les critères originaux d'inclusion et d'exclusion. RéSULTATS: Le nombre de personnes potentiellement éligibles pour les dix études s'est situé entre 2082 et 10 157. Les patient·es potentiellement admissibles en provenance d'unités de soins intensifs communautaires ont représenté 40,0 % de toutes les personnes potentiellement admissibles. Le recrutement de patient·es en provenance d'unités de soins intensifs communautaires aurait permis une hausse moyenne du recrutement potentiel de 64,0 %. L'inclusion de patient·es des unités de soins intensifs communautaires pourrait également réduire le temps nécessaire à la complétion des études de 14 mois en moyenne (réduction de 43 %). CONCLUSION: L'inclusion de patient·es en provenance d'unités de soins intensifs d'hôpitaux communautaires dans la recherche clinique en soins critiques a le potentiel d'augmenter substantiellement le recrutement et de diminuer le temps nécessaire à la complétion des études.

STOP Signs: A Population-based Interrupted Time Series Analysis of Antibiotic Duration for Complicated Intraabdominal Infection Before and After the Publication of a Landmark RCT.

OBJECTIVE: To determine if the STOP-IT randomized controlled trial changed antibiotic prescribing in patients with Complicated Intraabdominal Infection (CIAI). SUMMARY OF BACKGROUND DATA: CIAI is common and causes significant morbidity. In May 2015, the STOP-IT randomized controlled trial showed equivalent outcomes between four-day and clinically determined antibiotic duration. METHODS: This was a population-based retrospective cohort study using interrupted time series methods. The STOP-IT publication date was the exposure. Median duration of inpatient antibiotic prescription was the outcome. All adult patients admitted to four hospitals in Calgary, Canada between July 2012 and December 2018 with CIAI who survived at least four days following source control were included. Analysis was stratified by infectious source as appendix or biliary tract (group A) versus other (group B). RESULTS: Among 4384 included patients, clinical and demographic attributes were similar before vs after publication. In Group A, median inpatient antibiotic duration was 3 days and unchanged from the beginning to the end of the study period [adjusted median difference -0.00 days, 95% confidence interval (CI) -0.37 - 0.37 days]. In Group B, antibiotic duration was shorter at the end of the study period (7.87 vs 6.73 days; -1.14 days, CI-2.37 - 0.09 days), however there was no change in trend following publication (-0.03 days, CI -0.16 - 0.09). CONCLUSIONS: For appendiceal or biliary sources of CIAI, antibiotic duration was commensurate with the experimental arm of STOP-IT. For other sources, antibiotic duration was long and did not change in response to trial publication. Additional implementation science is needed to improve antibiotic stewardship.

Association Between Pandemic Coronavirus Disease 2019 Public Health Measures and Reduction in Critical Care Utilization Across ICUs in Alberta, Canada.

OBJECTIVES: The coronavirus disease 2019 pandemic has disrupted critical care services across the world. In anticipation of surges in the need for critical care services, governments implemented "lockdown" measures to preserve and create added critical care capacity. Herein, we describe the impact of lockdown measures on the utilization of critical care services and patient outcomes compared with nonlockdown epochs in a large integrated health region. DESIGN: This was a population-based retrospective cohort study. SETTING: Seventeen adult ICUs across 14 acute care hospitals in Alberta, Canada. PATIENTS: All adult (age ≥ 15 yr) patients admitted to any study ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure was ICU admission during "lockdown" occurring between March 16, 2020, and June 30, 2020. This period was compared with two nonpandemic control periods: "year prior" (March 16, 2019, to June 30, 2019) and "pre lockdown" immediately prior (November 30, 2019, to March 15, 2020). The primary outcome was the number of ICU admissions. Secondary outcomes included the following: daily measures of ICU utilization, ICU duration of stay, avoidable delay in ICU discharge, and occupancy; and patient outcomes. Mixed multilevel negative binomial regression and interrupted time series regression were used to compare rates of ICU admissions between periods. Multivariable regressions were used to compare patient outcomes between periods. During the lockdown, there were 3,649 ICU admissions (34.1 [8.0] ICU admissions/d), compared with 4,125 (38.6 [9.3]) during the prelockdown period and 3,919 (36.6 [8.7]) during the year prior. Mean bed occupancy declined significantly during the lockdown compared with the nonpandemic periods (78.7%, 95.9%, and 96.4%; p < 0.001). Avoidable ICU discharge delay also decreased significantly (42.0%, 53.2%, and 58.3%; p < 0.001). During the lockdown, patients were younger, had fewer comorbid diseases, had higher acuity, and were more likely to be medical admissions compared with the nonpandemic periods. Adjusted ICU and hospital mortality and ICU and hospital lengths of stay were significantly lower during the lockdown compared with nonpandemic periods. CONCLUSIONS: The coronavirus disease 2019 lockdown resulted in substantial changes to ICU utilization, including a reduction in admissions, occupancy, patient lengths of stay, and mortality.

Association Between Afterhours Discharge From the Intensive Care Unit and Hospital Mortality: A Multi-Center Retrospective Cohort Study.

BACKGROUND: There is conflicting evidence on the association between afterhours discharge from the intensive care unit (ICU) and hospital mortality. We examined the effects of afterhours discharge, including the potential effect of residual organ dysfunction, on hospital mortality in a large integrated health region. METHODS: We performed a multi-center retrospective cohort study of 10,463 adults discharged from 9 mixed medical/surgical ICUs in Alberta from June 2012 to December 2014. We applied a 2-stage modeling strategy to investigate the association between afterhours discharge (19:00h to 07:59h) and post-ICU hospital mortality. We applied mixed-effect multi-variable linear regression to assess the relationship between discharge organ dysfunction and afterhours discharge. We then applied mixed-effect multi-variable logistic regression to evaluate the direct, indirect and integrated associations of afterhours discharge on hospital mortality and hospitalization duration. RESULTS: Of 10,463 patients, 23.7% (n = 2,480) were discharged afterhours, of which 27.4% occurred on a holiday or weekend. This varied significantly by ICU size, type, and site. Patients discharged afterhours were more likely medical admissions, had greater multi-morbidity and illness acuity. A greater average SOFA score in the 72 hours prior to ICU discharge was not associated with afterhours discharge. However, a greater average SOFA score was associated with hospital mortality (adjusted-odds ratio [OR], 1.23; 95% CI, 1.18-1.28). Afterhours discharge was associated with higher hospital mortality (adjusted-OR, 1.19; 95% CI, 1.01-1.39), increased hospital stay (adjusted-risk ratio [RR], 1.10; 95% CI, 1.09-1.11) and increased post-ICU stay (adjusted-RR, 1.16; 95% CI, 1.14-1.17) when compared with workhours discharge. CONCLUSIONS: Afterhours discharge is common, occurring in 1 in 4 discharges, and is widely variable across ICUs. Patients discharged afterhours have greater risk of hospital mortality and prolonged hospitalization.

Needs Assessment Survey Identifying Research Processes Which may be Improved by Automation or Artificial Intelligence: ICU Community Modeling and Artificial Intelligence to Improve Efficiency (ICU-Comma).

BACKGROUND: Critical care research in Canada is conducted primarily in academically-affiliated intensive care units with established research infrastructure, including research coordinators (RCs). Recently, efforts have been made to engage community hospital ICUs in research albeit with barriers. Automation or artificial intelligence (AI) could aid the performance of routine research tasks. It is unclear which research study processes might be improved through AI automation. METHODS: We conducted a cross-sectional survey of Canadian ICU research personnel. The survey contained items characterizing opinions regarding research processes that may be amenable to AI automation. We distributed the questionnaire via email distribution lists of 3 Canadian research societies. Open-ended questions were analyzed using a thematic content analysis approach. RESULTS: A total of 49 survey responses were received (response rate: 8%). Tasks that respondents felt were time-consuming/tedious/tiresome included: screening for potentially eligible patients (74%), inputting data into case report forms (65%), and preparing internal tracking logs (53%). Tasks that respondents felt could be performed by AI automation included: screening for eligible patients (59%), inputting data into case report forms (55%), preparing internal tracking logs (51%), and randomizing patients into studies (45%). Open-ended questions identified enthusiasm for AI automation to improve information accuracy and efficiency while freeing up RCs to perform tasks that require human interaction. This enthusiasm was tempered by the need for proper AI education and oversight. CONCLUSIONS: There were balanced supportive (increased efficiency and re-allocation of tasks) and challenges (informational accuracy and oversight) with regards to AI automation in ICU research.

Avoidable intensive care unit resource use and costs of unvaccinated patients with COVID-19: a historical population-based cohort study.

PURPOSE: SARS-CoV-2 vaccines have been proven effective at preventing poor outcomes from COVID-19; however, voluntary vaccination rates have been suboptimal. We assessed the potential avoidable intensive care unit (ICU) resource use and associated costs had unvaccinated or partially vaccinated patients hospitalized with COVID-19 been fully vaccinated. METHODS: We conducted a retrospective, population-based cohort study of persons aged 12 yr or greater in Alberta (2021 population ~ 4.4 million) admitted to any ICU with COVID-19 from 6 September 2021 to 4 January 2022. We used publicly available aggregate data on COVID-19 infections, vaccination status, and health services use. Intensive care unit admissions, bed-days, lengths of stay, and costs were estimated for patients with COVID-19 and stratified by vaccination status. RESULTS: In total, 1,053 patients admitted to the ICU with COVID-19 were unvaccinated, 42 were partially vaccinated, and 173 were fully vaccinated (cumulative incidence 230.6, 30.8, and 5.5 patients/100,000 population, respectively). Cumulative incidence rate ratios of ICU admission were 42.2 (95% confidence interval [CI], 39.7 to 44.9) for unvaccinated patients and 5.6 (95% CI, 4.1 to 7.6) for partially vaccinated patients when compared with fully vaccinated patients. During the study period, 1,028 avoidable ICU admissions and 13,015 bed-days were recorded for unvaccinated patients and the total avoidable costs were CAD 61.3 million. The largest opportunity to avoid ICU bed-days and costs was in unvaccinated patients aged 50 to 69 yr. CONCLUSIONS: Unvaccinated patients with COVID-19 had substantially greater rates of ICU admissions, ICU bed-days, and ICU-related costs than vaccinated patients did. This increased resource use would have been potentially avoidable had these unvaccinated patients been vaccinated against SARS-CoV-2.

RéSUMé: OBJECTIF: Les vaccins contre le SRAS-CoV-2 se sont avérés efficaces pour prévenir les devenirs défavorables associés à la COVID-19; toutefois, les taux de vaccination volontaire ont été sous-optimaux. Nous avons évalué l'utilisation potentiellement évitable des ressources des unités de soins intensifs (USI) et les coûts associés si les patients non vaccinés ou partiellement vaccinés qui ont dû être hospitalisés pour la COVID-19 avaient été complètement vaccinés. MéTHODE: Nous avons réalisé une étude de cohorte rétrospective basée sur la population de personnes âgées de 12 ans ou plus en Alberta (population de 2021 ~ 4,4 millions) admises dans une unité de soins intensifs et atteintes de COVID-19 du 6 septembre 2021 au 4 janvier 2022. Nous avons utilisé des données agrégées accessibles au public sur les infections à la COVID-19, le statut vaccinal et l'utilisation des services de santé. Les admissions aux soins intensifs, les journées-patients, les durées de séjour et les coûts ont été estimés pour les patients atteints de la COVID-19 et stratifiés selon le statut vaccinal. RéSULTATS: Au total, 1053 patients admis à l'USI souffrant de la COVID-19 n'étaient pas vaccinés, 42 étaient partiellement vaccinés et 173 étaient complètement vaccinés (incidence cumulative 230,6, 30,8 et 5,5 patients / 100 000 habitants, respectivement). Les taux d'incidence cumulés des admissions aux soins intensifs étaient de 42,2 (intervalle de confiance [IC] à 95 %, 39,7 à 44,9) pour les patients non vaccinés et de 5,6 (IC 95 %, 4,1 à 7,6) pour les patients partiellement vaccinés par rapport aux patients entièrement vaccinés. Au cours de la période à l'étude, 1028 admissions évitables aux soins intensifs et 13 015 journées-patients ont été enregistrées pour les patients non vaccinés, et les coûts totaux évitables étaient de 61,3 millions de dollars canadiens. L'économie potentielle la plus importante en matière de journées-patients et de coûts en soins intensifs touchait les patients non vaccinés âgés de 50 à 69 ans. CONCLUSION: Les patients non vaccinés atteints de COVID-19 ont affiché des taux beaucoup plus élevés d'admissions à l'USI, de journées-patients à l'USI et de coûts liés à l'USI que les patients vaccinés. Cette utilisation accrue des ressources aurait été potentiellement évitable si ces patients non vaccinés avaient été vaccinés contre le SRAS-CoV-2.

Prone positioning for ARDS patients-tips for preparation and use during the COVID-19 pandemic.

Many patients with coronavirus disease (COVID-19) will develop acute respiratory distress syndrome (ARDS). Prone positioning is an important non-pharmacologic strategy that should be considered for all invasively ventilated patients with moderate to severe ARDS (including those with COVID-19). Prone positioning offers several physiologic and clinical benefits, including improving hypoxemia, matching ventilation with perfusion, reducing regional hyperinflation, and improving survival. To safely offer prone positioning, appropriate training, simulation, and health system planning should be undertaken. In this review, we offer ten tips, based on the Alberta provincial prone positioning strategy during COVID-19, to safely implement and improve the appropriate use of prone positioning. We provide special considerations for its use during the COVID-19 pandemic or future respiratory pandemics.

RéSUMé: De nombreux patients atteints de la maladie du coronavirus (COVID-19) développeront un syndrome de détresse respiratoire aiguë (SDRA, ARDS en anglais). Le positionnement ventral est une importante stratégie non pharmacologique qui devrait être envisagée pour tous les patients ventilés de manière invasive et souffrant d'un SDRA modéré à grave (y compris ceux atteints de la COVID-19). Le positionnement ventral offre plusieurs avantages physiologiques et cliniques, notamment l'amélioration de l'hypoxémie, une adéquation de la ventilation avec la perfusion, la réduction de l'hyperinflation régionale et l'amélioration de la survie. Pour offrir un positionnement ventral en toute sécurité, une formation, des simulations et une planification des ressources appropriées devraient être entreprises. Dans le cadre de ce compte rendu, nous proposons dix conseils, fondés sur la stratégie provinciale de positionnement ventral de l'Alberta au cours de la COVID-19, afin de mettre en œuvre et d'améliorer en toute sécurité l'utilisation appropriée du positionnement ventral. Nous décrivons des considérations particulières pour son utilisation pendant la pandémie de COVID-19 ou les futures pandémies respiratoires.

Describing organ dysfunction in the intensive care unit: a cohort study of 20,000 patients.

BACKGROUND: Multiple organ dysfunction is a common cause of morbidity and mortality in intensive care units (ICUs). Original development of the Sequential Organ Failure Assessment (SOFA) score was not to predict outcome, but to describe temporal changes in organ dysfunction in critically ill patients. Organ dysfunction scoring may be a reasonable surrogate outcome in clinical trials but further exploration of the impact of case mix on the temporal sequence of organ dysfunction is required. Our aim was to compare temporal changes in SOFA scores between hospital survivors and non-survivors. METHODS: We performed a population-based observational retrospective cohort study of critically ill patients admitted from January 1, 2004, to December 31, 2013, to 4 multisystem adult intensive care units (ICUs) in Calgary, Canada. The primary outcome was temporal changes in daily SOFA scores during the first 14 days of ICU admission. SOFA scores were modeled between hospital survivors and non-survivors using generalized estimating equations (GEE) and were also stratified by admission SOFA (≤ 11 versus > 11). RESULTS: The cohort consisted of 20,007 patients with at least one SOFA score and was mostly male (58.2%) with a median age of 59 (interquartile range [IQR] 44-72). Median ICU length of stay was 3.5 (IQR 1.7-7.5) days. ICU and hospital mortality were 18.5% and 25.5%, respectively. Temporal change in SOFA scores varied by survival and admission SOFA score in a complicated relationship. Area under the receiver operating characteristic (ROC) curve using admission SOFA as a predictor of hospital mortality was 0.77. The hospital mortality rate was 5.6% for patients with an admission SOFA of 0-2 and 94.4% with an admission SOFA of 20-24. There was an approximately linear increase in hospital mortality for SOFA scores of 3-19 (range 8.7-84.7%). CONCLUSIONS: Examining the clinical course of organ dysfunction in a large non-selective cohort of patients provides insight into the utility of SOFA. We have demonstrated that hospital outcome is associated with both admission SOFA and the temporal rate of change in SOFA after admission. It is necessary to further explore the impact of additional clinical factors on the clinical course of SOFA with large datasets.

Implementation of population-level screening for frailty among patients admitted to adult intensive care in Alberta, Canada.

PURPOSE: A substantial proportion of patients admitted to intensive care units (ICUs) are frail; however, the epidemiology of frailty has not been explored at a population-level. Following implementation of a validated frailty measure into a provincial ICU clinical information system, we describe the population-based prevalence and outcomes of frailty in patients admitted to ICUs. METHODS: Retrospective cohort study of adult admissions to 17 ICUs. Data were captured using eCritical Alberta. A Clinical Frailty Scale (CFS) score assigned at ICU admission was used to define the exposure (CFS score ≥ 5). Primary outcome was hospital mortality. Secondary outcomes were ICU and hospital stay, and receipt of organ support. RESULTS: Fifteen thousand two hundred and thirty-eight patients (81%) were assigned a CFS score at ICU admission. Of these, 28% (95% confidence interval [CI], 27 to 28) were frail. Prevalence of frailty was 9-43% across ICUs. Frail patients were older [mean (standard deviation) 63 (15) vs 56 (17) yr; P < 0.001], more likely to be male (54% vs 46% female; P < 0.001), and had higher APACHE II scores [22 (8) vs 17 (8); P < 0.001] compared with non-frail patients. Frail patients received less mechanical ventilation (62% vs 68%; P < 0.001) and vasoactive therapy (24% vs 57%; P < 0.001), but more non-invasive ventilation (22% vs 9%; P < 0.001). Frail patients had higher hospital mortality (23% vs 9%; adjusted odds ratio, 1.80; 95% CI, 1.64 to 2.05, along with longer ICU stay (median [interquartile range] 4 [2-8] vs 3 [2-6] days; P < 0.001), and longer hospital stay (16 [8-36] vs 10 [5-20] days; P < 0.001) compared with non-frail patients. CONCLUSION: A validated measure of frailty can be implemented at the population level in ICU. Frailty is common in ICU patients and has implications for health service use and clinical outcomes.

Association between afterhours admission to the intensive care unit, strained capacity, and mortality: a retrospective cohort study.

BACKGROUND: Admission to the intensive care unit (ICU) outside daytime hours has been shown to be variably associated with increased morbidity and mortality. We aimed to describe the characteristics and outcomes of patients admitted to the ICU afterhours (22:00-06:59 h) in a large Canadian health region. We further hypothesized that the association between afterhours admission and mortality would be modified by indicators of strained ICU capacity. METHODS: This is a population-based cohort study of 12,265 adults admitted to nine ICUs in Alberta from June 2012 to December 2014. We used a path-analysis modeling strategy and mixed-effects multivariate regression analysis to evaluate direct and integrated associations (mediated through Acute Physiology and Chronic Health Evaluation (APACHE) II score) between afterhours admission (22:00-06:59 h) and ICU mortality. Further analysis examined the effects of strained ICU capacity and varied definitions of afterhours and weekend admissions. ICU occupancy ≥ 90% or clustering of admissions (≥ 0.15, defined as number of admissions 2 h before or after the index admission, divided by the number of ICU beds) were used as indicators of strained capacity. RESULTS: Of 12,265 admissions, 34.7% (n = 4251) occurred afterhours. The proportion of afterhours admissions varied amongst ICUs (range 26.7-37.8%). Patients admitted afterhours were younger (median (IQR) 58 (44-70) vs 60 (47-70) years, p < 0.0001), more likely to have a medical diagnosis (75.9% vs 72.1%, p < 0.0001), and had higher APACHE II scores (20.9 (8.6) vs 19.9 (8.3), p < 0.0001). Crude ICU mortality was greater for those admitted afterhours (15.9% vs 14.1%, p = 0.007), but following multivariate adjustment there was no direct or integrated effect on ICU mortality (odds ratio (OR) 1.024; 95% confidence interval (CI) 0.923-1.135, p = 0.658). Furthermore, direct and integrated analysis showed no association of afterhours admission and hospital mortality (p = 0.90) or hospital length of stay (LOS) (p = 0.27), although ICU LOS was shorter (p = 0.049). Early-morning admission (00:00-06:59 h) with ICU occupancy ≥ 90% was associated with short-term (≤ 7 days) and all-cause ICU mortality. CONCLUSIONS: One-third of critically ill patients are admitted to the ICU afterhours. Afterhours ICU admission was not associated with greater mortality risk in most circumstances but was sensitive to strained ICU capacity.

Antibiotic Utilization Patterns in Patients with Ventilator-Associated Pneumonia: A Canadian Context.

This retrospective cohort study describes the patterns of antibiotic use for the treatment of ventilator-associated pneumonia (VAP) in the Calgary Zone of Alberta Health Services. Timing, appropriateness, and duration of antibiotics were evaluated in two hundred consecutive cases of VAP derived from 4 adult intensive care units (ICU). Antibiotic therapy was initiated in less than 24 hours from VAP diagnosis in 83% of cases. Although most patients (89%) received empiric therapy that demonstrated in vitro sensitivity to the identified pathogens, only 24% of cases were congruent with the 2008 Association of Medical Microbiology and Infectious Disease (AMMI) guidelines. Both ICU (p = 0.001) and hospital (p = 0.015) mortality were significantly lower and there was a trend for shorter ICU length of stay (p = 0.051) in patients who received appropriate versus inappropriate initial antibiotics. There were no outcome differences related to compliance with AMMI guidelines. This exploratory study provides insight into the use of antimicrobials for the treatment of VAP in a large Canadian health region. The discordance between the assessments of appropriateness of empiric therapy based on recovered pathogens versus AMMI guidelines is notable, emphasizing the importance of using as much as possible local microbiologic and antimicrobial resistance data.

Divergent expiratory braking activity of costal and crural diaphragm.

BACKGROUND: There is increasing clinical interest in understanding the contribution of the diaphragm in early expiration, especially during mechanical ventilation. However, current experimental evidence is limited, so essential activity of the diaphragm during expiration and diaphragm segmental differences in expiratory activity, are unknown. OBJECTIVES: To determine if: 1) the diaphragm is normally active into expiration during spontaneous breathing and hypercapnic ventilation, 2) expiratory diaphragmatic activity is distributed equally among the segments of the diaphragm, costal and crural. METHODS: In 30 spontaneously breathing male and female canines, awake without confounding anesthetic, we measured directly both inspiratory and expiratory electrical activity (EMG), and corresponding mechanical shortening, of costal and crural diaphragm, during room air and hypercapnia. RESULTS: During eupnea, costal and crural diaphragm are active into expiration, showing significant and distinct expiratory activity, with crural expiratory activity greater than costal, for both magnitude and duration. This diaphragm segmental difference diverged further during progressive hypercapnic ventilation: crural expiratory activity progressively increased, while costal expiratory activity disappeared. CONCLUSION: The diaphragm is not passive during expiration. During spontaneous breathing, expiratory activity -"braking"- of the diaphragm is expressed routinely, but is not equally distributed. Crural muscle "braking" is greater than costal muscle in magnitude and duration. With increasing ventilation during hypercapnia, expiratory activity -"braking"- diverges notably. Crural expiratory activity greatly increases, while costal expiratory "braking" decreases in magnitude and duration, and disappears. Thus, diaphragm expiratory "braking" action represents an inherent, physiological function of the diaphragm, distinct for each segment, expressing differing neural activation.

Multicentre implementation of a quality improvement initiative to reduce delirium in adult intensive care units: An interrupted time series analysis.

PURPOSE: The ABCDEF bundle may improve delirium outcomes among intensive care unit (ICU) patients, however population-based studies are lacking. In this study we evaluated effects of a quality improvement initiative based on the ABCDEF bundle in adult ICUs in Alberta, Canada. MATERIAL AND METHODS: We conducted a pre-post, registry-based clinical trial, analysed using interrupted time series methodology. Outcomes were examined via segmented linear regression using mixed effects models. The main data source was a population-based electronic health record. RESULTS: 44,405 consecutive admissions (38,400 unique patients) admitted to 15 general medical/surgical and/or neurologic adult ICUs between 2014 and 2019 were included. The proportion of delirium days per ICU increased from 30.24% to 35.31% during the pre-intervention period. After intervention implementation it decreased significantly (bimonthly decrease of 0.34%, 95%CI 0.18-0.50%, p < 0.01) from 33.48% (95%CI 29.64-37.31%) in 2017 to 28.74% (95%CI 25.22-32.26%) in 2019. The proportion of sedation days using midazolam demonstrated an immediate decrease of 7.58% (95%CI 4.00-11.16%). There were no significant changes in duration of invasive ventilation, proportion of partial coma days, ICU mortality, or potential adverse events. CONCLUSIONS: An ABCDEF delirium initiative was implemented on a population-basis within adult ICUs and was successful at reducing the prevalence of delirium.

Incidence of neurologic death among patients with brain injury: a cohort study in a Canadian health region.

BACKGROUND: Hospital mortality has decreased over time for critically ill patients with various forms of brain injury. We hypothesized that the proportion of patients who progress to neurologic death may have also decreased. METHODS: We performed a prospective cohort study involving consecutive adult patients with traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage or anoxic brain injury admitted to regional intensive care units in southern Alberta over a 10.5-year period. We used multivariable logistic regression to adjust for patient age and score on the Glasgow Coma Scale at admission, and to assess whether the proportion of patients who progress to neurologic death has changed over time. RESULTS: The cohort consisted of 2788 patients. The proportion of patients who progressed to neurologic death was 8.1% at the start of the study period, and the adjusted odds of progressing to neurologic death decreased over the study period (odds ratio [OR] per yr 0.92, 95% confidence interval [CI] 0.87-0.98, p = 0.006). This change was most pronounced among patients with traumatic brain injury (OR per yr 0.87, 95% CI 0.78-0.96, p = 0.005); there was no change among patients with anoxic injury (OR per yr 0.96, 95% CI 0.85-1.09, p = 0.6). A review of the medical records suggests that missed cases of neurologic death were rare (≤ 0.5% of deaths). INTERPRETATION: The proportion of patients with brain injury who progress to neurologic death has decreased over time, especially among those with head trauma. This finding may reflect positive developments in the prevention and care of brain injury. However, organ donation after neurologic death represents the major source of organs for transplantation. Thus, these findings may help explain the relatively stagnant rates of deceased organ donation in some regions of Canada, which in turn has important implications for the care of patients with end-stage organ failure.

A population-based assessment of avoidable hospitalizations and resource use of non-vaccinated patients with COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has precipitated a prolonged public health crisis. Numerous public health protections were widely implemented. The availability of effective and safe vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presented an opportunity to resolve this crisis; however, vaccine uptake was slow and inconsistent. This study evaluated the potential for preventable hospitalizations and avoidable resource use among eligible non-vaccinated persons hospitalized for COVID-19 had these persons been vaccinated. METHODS: This was a retrospective, population-based cohort study. The population-at-risk were persons aged ≥ 12 years in Alberta (mid-year 2021 population ~ 4.4 million). The primary exposure was vaccination status. The primary outcome was hospitalization with confirmed SARS-CoV-2, and secondary outcomes included avoidable hospitalizations, avoidable hospital bed-days, and the potential cost avoidance related to COVID-19. The study inception period was 27 September 2021 to 25 January 2022. Data on COVID-19 hospitalizations, vaccination status, health services, and costs were obtained from the Government of Alberta and from the Discharge Abstract Database. RESULTS: Hospitalizations occurred in 3835, 1907, and 481 persons who were non-vaccinated, fully vaccinated, and boosted (risk of hospitalization/100,000 population: 886, 92, and 43), respectively. For non-vaccinated persons compared with fully vaccinated and boosted persons, the risk ratios (95%CI) of hospitalization were 9.7 (7.9-11.8) and 20.6 (17.9-23.6), respectively. For non-vaccinated persons, estimates of avoidable hospitalizations and bed-days used were 3439 and 36,331 if fully vaccinated and 3764 and 40,185 if boosted. Estimates of cost avoidance for non-vaccinated persons were $101.46 million if fully vaccinated and $110.24 million if boosted. CONCLUSION: Eligible non-vaccinated persons with COVID-19 had tenfold and 21-fold higher risks of hospitalization relative to whether they had been fully vaccinated or boosted, resulting in considerable avoidable hospital bed-days and costs.

RéSUMé: OBJECTIF: La pandémie de maladie à coronavirus 2019 (COVID-19) a précipité une crise de santé publique prolongée. De nombreuses mesures de protection de la santé publique ont été appliquées à grande échelle. La disponibilité de vaccins sûrs et efficaces contre le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) a présenté une occasion de résoudre la crise, mais l'acceptation de la vaccination a été lente et inégale. Dans cette étude, nous évaluons le potentiel d'hospitalisations évitables et d'utilisation évitable des ressources pour les personnes non vaccinées admissibles hospitalisées pour la COVID-19, si ces personnes avaient été vaccinées. MéTHODES: Il s'agissait d'une étude de cohorte populationnelle rétrospective. La population à risque était les personnes de ≥ 12 ans en Alberta (~ 4,4 millions au milieu de l'année 2021). Le principal risque était le statut vaccinal. Le principal résultat clinique était l'hospitalisation avec SRAS-CoV-2 confirmé, et les résultats cliniques secondaires étaient les hospitalisations évitables, les jours-lits à l'hôpital évitables et l'évitement potentiel des coûts liés à la COVID-19. La période initiale de l'étude s'est étendue du 27 septembre 2021 au 25 janvier 2022. Les données sur les hospitalisations pour la COVID-19, le statut vaccinal, les coûts et les services de santé provenaient du gouvernement de l'Alberta et de la Base de données sur les congés des patients. RéSULTATS: En tout, 3 835 personnes non vaccinées, 1 907 personnes ayant reçu tous leurs vaccins et 481 personnes ayant reçu des doses de rappel ont été hospitalisées (risque d'hospitalisation p. 100 000 personnes : 886, 92 et 43, respectivement). Pour les personnes non vaccinées, comparativement aux personnes ayant reçu tous leurs vaccins et/ou les doses de rappel, les risques relatifs d'hospitalisation (IC de 95%) étaient de 9,7 (7,9­11,8) et de 20,6 (17,9­23,6), respectivement. Selon nos estimations, les personnes non vaccinées auraient évité 3 439 hospitalisations et 36 331 jours-lits si elles avaient reçu tous leurs vaccins, et 3 764 hospitalisations et 40 185 jours-lits si elles avaient en plus reçu les doses de rappel. Nous avons aussi estimé que les personnes non vaccinées auraient évité des coûts de 101,46 millions de dollars si elles avaient reçu tous leurs vaccins et de 110,24 millions de dollars si elles avaient en plus reçu les doses de rappel. CONCLUSION: Les personnes non vaccinées admissibles ayant contracté la COVID-19 ont présenté un risque d'hospitalisation 10 fois plus élevé que si elles avaient reçu tous leurs vaccins et 21 fois plus élevé que si elles avaient en plus reçu les doses de rappel, ce qui représente des jours-lits à l'hôpital et des coûts évitables considérables.

Designing a Behaviour Change Wheel guided implementation strategy for a hypoxaemic respiratory failure and ARDS care pathway that targets barriers.

BACKGROUND: A significant gap exists between ideal evidence-based practice and real-world application of evidence-informed therapies for patients with hypoxaemic respiratory failure (HRF) and acute respiratory distress syndrome (ARDS). Pathways can improve the quality of care provided by helping integrate and organise the use of evidence informed practices, but barriers exist that can influence their adoption and successful implementation. We sought to identify barriers to the implementation of a best practice care pathway for HRF and ARDS and design an implementation science-based strategy targeting these barriers that is tailored to the critical care setting. METHODS: The intervention assessed was a previously described multidisciplinary, evidence-based, stakeholder-informed, integrated care pathway for HRF and ARDS. A survey questionnaire (12 open text questions) was administered to intensive care unit (ICU) clinicians (physicians, nurses, respiratory therapists) in 17 adult ICUs across Alberta. The Behaviour Change Wheel, capability, opportunity, motivation - behaviour components, and Theoretical Domains Framework (TDF) were used to perform qualitative analysis on open text responses to identify barriers to the use of the pathway. Behaviour change technique (BCT) taxonomy, and Affordability, Practicality, Effectiveness and cost-effectiveness, Acceptability, Side effects and safety and Equity (APEASE) criteria were used to design an implementation science-based strategy specific to the critical care context. RESULTS: Survey responses (692) resulted in 16 belief statements and 9 themes with 9 relevant TDF domains. Differences in responses between clinician professional group and hospital setting were common. Based on intervention functions linked to each belief statement and its relevant TDF domain, 26 candidate BCTs were identified and evaluated using APEASE criteria. 23 BCTs were selected and grouped to form 8 key components of a final strategy: Audit and feedback, education, training, clinical decision support, site champions, reminders, implementation support and empowerment. The final strategy was described using the template for intervention description and replication framework. CONCLUSIONS: Barriers to a best practice care pathway were identified and were amenable to the design of an implementation science-based mitigation strategy. Future work will evaluate the ability of this strategy to improve quality of care by assessing clinician behaviour change via better adherence to evidence-based care.

Methods for determination of optimal positive end-expiratory pressure: a protocol for a scoping review.

INTRODUCTION: Titrated application of positive end-expiratory pressure (PEEP) is an important part of any mechanical ventilation strategy. However, the method by which the optimal PEEP is determined and titrated varies widely. Methods for determining optimal PEEP have been assessed using a variety of different study designs and patient populations. We will conduct a scoping review to systematically identify all methods for determining optimal PEEP, and to identify the patient populations, outcomes measured and study designs used for each method. The goal will be to identify gaps in the optimal PEEP literature and identify areas where there may be an opportunity to further systematically synthesise and meta-analyse existing literature. METHODS AND ANALYSIS: Using scoping review methodology, we will generate a comprehensive search strategy based on inclusion and exclusion criteria generated using the population, concept, context framework. Five different databases will be searched (MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus). Three investigators will independently screen titles and abstracts, and two investigators will independently complete full-text review and data extraction. Included citations will be categorised in terms of PEEP method, study design, patient population and outcomes measured. The methods for PEEP titration will be described in detail, including strengths and limitations. ETHICS AND DISSEMINATION: Given this is a synthesis of existing literature, ethics approval is not required. The results will be disseminated to stakeholders via presentation at local, regional and national levels, as well as publication in a high-impact critical care journal. There is also the potential to impact local clinical care protocols and inform broader clinical practice guidelines undertaken by societies.

Protocol and statistical analysis plan for the identification and treatment of hypoxemic respiratory failure and acute respiratory distress syndrome with protection, paralysis, and proning: A type-1 hybrid stepped-wedge cluster randomised effectiveness-implementation study.

Objective: To describe a study protocol and statistical analysis plan (SAP) for the identification and treatment of hypoxemic respiratory failure (HRF) and acute respiratory distress syndrome (ARDS) with protection, paralysis, and proning (TheraPPP) study prior to completion of recruitment, electronic data retrieval, and analysis of any data. Design: TheraPPP is a stepped-wedge cluster randomised study evaluating a care pathway for HRF and ARDS patients. This is a type-1 hybrid effectiveness-implementation study design evaluating both intervention effectiveness and implementation; however primarily powered for the effectiveness outcome. Setting: Seventeen adult intensive care units (ICUs) across Alberta, Canada. Participants: We estimate a sample size of 18816 mechanically ventilated patients, with 11424 patients preimplementation and 7392 patients postimplementation. We estimate 2688 sustained ARDS patients within our study cohort. Intervention: An evidence-based, stakeholder-informed, multidisciplinary care pathway called Venting Wisely that standardises diagnosis and treatment of HRF and ARDS patients. Main outcome measures: The primary outcome is 28-day ventilator-free days (VFDs). The primary analysis will compare the mean 28-day VFDs preimplementation and postimplementation using a mixed-effects linear regression model. Prespecified subgroups include sex, age, HRF, ARDS, COVID-19, cardiac surgery, body mass index, height, illness acuity, and ICU volume. Results: This protocol and SAP are reported using the Standard Protocol Items: Recommendations for Interventional Trials guidance and the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. The study received ethics approval and was registered (ClinicalTrials.gov-NCT04744298) prior to patient enrolment. Conclusions: TheraPPP will evaluate the effectiveness and implementation of an HRF and ARDS care pathway.