Patient-important upper gastrointestinal bleeding in the ICU: A mixed-methods study of patient and family perspectives.

INTRODUCTION: The objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial. DESIGN: This was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding. SETTING: Canada and the United States. PARTICIPANTS: 51 ICU survivors and family members of ICU patients. RESULTS: Participants considered gastrointestinal bleeding to be important if it resulted in death, disability, or prolonged hospitalization. The following also signaled patient-important upper gastrointestinal bleeding: blood transfusion, vasopressors, endoscopy, CT-angiography, or surgery. Whether an intervention evinced concern depended on its effectiveness, side-effects, invasiveness and accessibility; contextual influences included participant familiarity and knowledge of interventions and trust in the clinical team. CONCLUSIONS: Survivors of critical illness and family members described patient-important upper gastrointestinal bleeding differently than current definitions of clinically-important upper gastrointestinal bleeding.

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.

Does pain optimisation impact delirium outcomes in critically ill patients? A systematic review and meta-analysis protocol.

BACKGROUND: Untreated pain is associated with short-term and long-term consequences, including post-traumatic stress disorder and insomnia. Side effects of some analgesic medications include dysphoria, hallucinations and delirium. Therefore, both untreated pain and analgesic medications may be risk factors for delirium. Delirium is associated with longer length of stay or cognitive impairment. Our systematic review and meta-analysis will examine the relationship between pain or analgesic medications with delirium occurrence, duration and severity among critically ill adults. METHODS AND ANALYSIS: MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials and a review of recent conference abstracts will be searched without restriction from inception to 15 May 2023. Study inclusion criteria are: (1) age≥18 years admitted to intensive care; (2) report a measure of pain, analgesic medications and delirium; (3) study design-randomised controlled trial, quasiexperimental designs and observational cohort and case-control studies excluding case reports. Study exclusion criteria are: (1) alcohol withdrawal delirium or delirium tremens; or (2) general anaesthetic emergence delirium; or (3) lab or animal studies. Risk of bias will be assessed with the Risk of Bias V.2 and risk of bias in non-randomised studies tools. There is no language restriction. Occurrence estimates will be transformed using the Freeman-Tukey double arcsine. Point estimates will be pooled using Hartung-Knapp Sidik-Jonkman random effects meta-analysis to estimate a pooled risk ratio. Statistical heterogeneity will be estimated with the I2 statistic. Risk of small study effects will be assessed using funnel plots and Egger test. Studies will be analysed for time-varying and unmeasured confounding using E values. ETHICS AND DISSEMINATION: Ethical approval is not required as this is an analysis of published aggregated data. We will share our findings at conferences and in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: The finalised protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022367715).

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.

Follow-up Care of Critically Ill Patients With Acute Kidney Injury: A Cohort Study.

Rationale & Objective: To evaluate follow-up care of critically ill patients with acute kidney injury (AKI). Study Design: Retrospective cohort study. Setting & Participants: Patients admitted to the intensive care unit (ICU) with AKI in Alberta, Canada from 2005 to 2018, who survived to discharge without kidney replacement therapy or estimated glomerular filtration rate <15 mL/min/1.73 m2. Exposure: AKI (defined as ≥50% or ≥0.3 mg/dL serum creatinine increase). Outcomes: The primary outcome was the cumulative incidence of an outpatient serum creatinine and urine protein measurement at 3 months postdischarge. Secondary outcomes included an outpatient serum creatinine or urine protein measurement or a nephrologist visit at 3 months postdischarge. Analytical Approach: Patients were followed from hospital discharge until the first of each outcome of interest, death, emigration from the province, kidney replacement therapy (maintenance dialysis or kidney transplantation), or end of study period (March 2019). We used non-parametric methods (Aalen-Johansen) to estimate the cumulative incidence functions of outcomes accounting for competing events (death and kidney replacement therapy). Results: There were 29,732 critically ill adult patients with AKI. The median age was 68 years (IQR, 57-77), 39% were female, and the median baseline estimated glomerular filtration rate was 72 mL/min/1.73 m2 (IQR, 53-90). The cumulative incidence of having an outpatient creatinine and urine protein measurement at 3 months postdischarge was 25% (95% CI, 25-26). At 3 months postdischarge, 64% (95% CI, 64-65) had an outpatient creatinine measurement, 28% (95% CI, 27-28) had a urine protein measurement, and 5% (95% CI, 4-5) had a nephrologist visit. Limitations: We lacked granular data, such as urine output. Conclusions: Many critically ill patients with AKI do not receive the recommended follow-up care. Our findings highlight a gap in the transition of care for survivors of critical illness and AKI.

What counts as patient-important upper gastrointestinal bleeding in the ICU? A mixed-methods study protocol of patient and family perspectives.

INTRODUCTION: Clinically important upper gastrointestinal bleeding is conventionally defined as bleeding accompanied by haemodynamic changes, requiring red blood cell transfusions or other invasive interventions. However, it is unclear if this clinical definition reflects patient values and preferences. This protocol describes a study to elicit views from patients and families regarding features, tests, and treatments for upper gastrointestinal bleeding that are important to them. METHODS AND ANALYSIS: This is a sequential mixed-methods qualitative-dominant multi-centre study with an instrument-building aim. We developed orientation tools and educational materials in partnership with patients and family members, including a slide deck and executive summary. We will invite intensive care unit (ICU) survivors and family members of former ICU patients to participate. Following a virtual interactive presentation, participants will share their perspectives in an interview or focus group. Qualitative data will be analysed using inductive qualitative content analysis, wherein codes will be derived directly from the data rather than using preconceived categories. Concurrent data collection and analysis will occur. Quantitative data will include self-reported demographic characteristics. This study will synthesise the values and perspectives of patients and family members to create a new trial outcome for a randomised trial of stress ulcer prophylaxis. This study is planned for May 2022 to August 2023. The pilot work was completed in Spring 2021. ETHICS AND DISSEMINATION: This study has ethics approval from McMaster University and the University of Calgary. Findings will be disseminated via manuscript and through incorporation as a secondary trial outcome on stress ulcer prophylaxis. TRIAL REGISTRATION NUMBER: NCT05506150.

Facilitators and Barriers Influencing Antipsychotic Medication Prescribing and Deprescribing Practices in Critically Ill Adult Patients: a Qualitative Study.

BACKGROUND: Antipsychotic medications do not alter the incidence or duration of delirium, but these medications are frequently prescribed and continued at transitions of care in critically ill patients when they may no longer be necessary or appropriate. OBJECTIVE: The purpose of this study was to identify and describe relevant domains and constructs that influence antipsychotic medication prescribing and deprescribing practices among physicians, nurses, and pharmacists that care for critically ill adult patients during and following critical illness. DESIGN: We conducted qualitative semi-structured interviews with critical care and ward healthcare professionals including physicians, nurses, and pharmacists to understand antipsychotic prescribing and deprescribing practices for critically ill adult patients during and following critical illness. PARTICIPANTS: Twenty-one interviews were conducted with 11 physicians, five nurses, and five pharmacists from predominantly academic centres in Alberta, Canada, between July 6 and October 29, 2021. MAIN MEASURES: We used deductive thematic analysis using the Theoretical Domains Framework (TDF) to identify and describe constructs within relevant domains. KEY RESULTS: Seven TDF domains were identified as relevant from the analysis: Social/Professional role and identity; Beliefs about capabilities; Reinforcement; Motivations and goals; Memory, attention, and decision processes; Environmental context and resources; and Beliefs about consequences. Participants reported antipsychotic prescribing for multiple indications beyond delirium and agitation including patient and staff safety, sleep management, and environmental factors such as staff availability and workload. Participants identified potential antipsychotic deprescribing strategies to reduce ongoing antipsychotic medication prescriptions for critically ill patients including direct communication tools between prescribers at transitions of care. CONCLUSIONS: Critical care and ward healthcare professionals report several factors influencing established antipsychotic medication prescribing practices. These factors aim to maintain patient and staff safety to facilitate the provision of care to patients with delirium and agitation limiting adherence to current guideline recommendations.

Clostridioides difficile infection in mechanically ventilated critically ill patients: A nested cohort study.

INTRODUCTION: Clostridioides difficile infection (CDI) is a serious complication of critical illness. The objective of the study was to determine its incidence, prevalence, timing, severity, predictors, and outcomes. METHODS: We performed a prospective nested cohort study of CDI within a randomized trial comparing Lactobacillus rhamnosus GG to placebo. We adjudicated cases of CDI using standardized definitions, assessed timing (pre-ICU, in ICU, post-ICU) and severity. We analyzed risk factors and outcomes. RESULTS: Of 2650 patients, 86 were diagnosed with CDI during 90,833 hospital-days (0.95/1000 hospital-days); CDI prevalence was 3.2%. CDI incidence varied in timing; 0.3% patients had CDI pre-ICU, 2.2% in the ICU; an 0.8% developed CDI post-ICU. Relapse or recurrence of CDI was documented in 9.3% patients. Infections were mild/moderate in severity. Complications included septic shock (26.7%), organ failure (16.3%), and toxic megacolon requiring colectomy (1.2%). No risk factors for CDI were identified. CDI was not associated with hospital mortality. The duration of hospital stay was longer for those who had CDI compared those who did not, CONCLUSION: CDI was uncommon, severity was mild to moderate and not associated with mortality however CDI was associated with a longer hospital stay.

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.

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.

A National Modified Delphi Consensus Process to Prioritize Experiences and Interventions for Antipsychotic Medication Deprescribing Among Adult Patients With Critical Illness.

Antipsychotic medications are frequently prescribed to critically ill patients leading to their continuation at transitions of care thereafter. The aim of this study was to generate evidence-informed consensus statements with key stakeholders on antipsychotic minimization and deprescribing for ICU patients. DESIGN: We completed three rounds of surveys in a National modified Delphi consensus process. During rounds 1 and 2, participants used a 9-point Likert scale (1-strongly disagree, 9-strongly agree) to rate perceptions related to antipsychotic prescribing (i.e., experiences regarding delivery of patient care), knowledge and frequency of antipsychotic use, knowledge surrounding antipsychotic guideline recommendations, and strategies (i.e., interventions addressing current antipsychotic prescribing practices) for antipsychotic minimization and deprescribing. Consensus was defined as a median score of 1-3 or 7-9. During round 3, participants ranked statements on antipsychotic minimization and deprescribing strategies that achieved consensus (median score 7-9) using a weighted ranking scale (0-100 points) to determine priority. SETTING: Online surveys distributed across Canada. SUBJECTS: Fifty-seven stakeholders (physicians, nurses, pharmacists) who work with ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants prioritized six consensus statements on strategies for consideration when developing and implementing interventions to guide antipsychotic minimization and deprescribing. Statements focused on limiting antipsychotic prescribing to patients: 1) with hyperactive delirium, 2) at risk to themselves, their family, and/or staff due to agitation, and 3) whose care and treatment are being impacted due to agitation or delirium, and prioritizing 4) communication among staff about antipsychotic effectiveness, 5) direct and efficient communication tools on antipsychotic deprescribing at transitions of care, and 6) medication reconciliation at transitions of care. CONCLUSIONS: We engaged diverse stakeholders to generate evidence-informed consensus statements regarding antipsychotic prescribing perceptions and practices that can be used to implement interventions to promote antipsychotic minimization and deprescribing strategies for ICU patients with and following critical illness.

Health economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): a cost-effectiveness analysis.

PURPOSE: We sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT). METHODS: We conducted a health economic evaluation alongside the PROSPECT randomized control trial (October 2013-March 2019). We adopted a public healthcare payer's perspective. Forty-four intensive care units in three countries (Canada/USA/Saudi Arabia) with adult critically ill, mechanically ventilated patients (N = 2,650) were included. Interventions were probiotics (Lactobacillus rhamnosus GG) vs placebo administered enterally twice daily. We collected healthcare resource use and estimated unit costs in 2019 United States dollars (USD) over a time horizon from randomization to hospital discharge/death. We calculated incremental cost-effectiveness ratios (ICERs) comparing probiotics vs usual care. The primary outcome was incremental cost per ventilator-associated pneumonia (VAP) event averted; secondary outcomes were costs per Clostridioides difficile-associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD), and mortality averted. Uncertainty was investigated using nonparametric bootstrapping and sensitivity analyses. RESULTS: Mean (standard deviation [SD]) cost per patient was USD 66,914 (91,098) for patients randomized to probiotics, with a median [interquartile range (IQR)] of USD 42,947 [22,239 to 76,205]. By comparison, for those not receiving probiotics, mean (SD) cost per patient was USD 62,701 (78,676) (median [IQR], USD 41,102 [23,170 to 75,140]; incremental cost, USD 4,213; 95% confidence interval [CI], -2,269 to 10,708). Incremental cost-effectiveness ratios for VAP or AAD events averted, probiotics were dominated by usual care (more expensive, with similar effectiveness). The ICERs were USD 1,473,400 per CDAD event averted (95% CI, undefined) and USD 396,764 per death averted (95% CI, undefined). Cost-effectiveness acceptability curves reveal that probiotics were not cost-effective across wide ranges of plausible willingness-to-pay thresholds. Sensitivity analyses did not change the conclusions. CONCLUSIONS: Probiotics for VAP prevention among critically ill patients were not cost-effective. Study registration data www. CLINICALTRIALS: gov (NCT01782755); registered 4 February 2013.

RéSUMé: OBJECTIF: Nous avons cherché à comparer le rapport coût-efficacité d'un traitement avec probiotiques ajoutés aux soins habituels avec des soins habituels prodigués sans probiotiques chez les patients des soins intensifs sous ventilation mécanique dans le cadre de l'étude PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial). MéTHODE: Nous avons réalisé une évaluation de l'économie de la santé parallèlement à l'étude randomisée contrôlée PROSPECT (octobre 2013-mars 2019). Nous avons adopté le point de vue d'un payeur public de services de santé. Quarante-quatre unités de soins intensifs dans trois pays (Canada/États-Unis/Arabie saoudite) prenant soin de patients adultes gravement malades sous ventilation mécanique (n = 2650) ont été inclus. Les interventions ont été les suivantes : probiotiques (Lactobacillus rhamnosus GG) vs placebo administrés par voie entérale deux fois par jour. Nous avons recueilli les données concernant l'utilisation des ressources en soins de santé et estimé les coûts unitaires en dollars américains (USD) de 2019 sur un horizon temporel allant de la randomisation au congé de l'hôpital / décès. Nous avons calculé des rapports coût-efficacité différentiels (RCED) en comparant les probiotiques vs les soins habituels. Le critère d'évaluation principal était le coût différentiel par événement évité de pneumonie associée au ventilateur (PAV); les critères d'évaluation secondaires étaient les coûts par diarrhée associée au Clostridioides difficile (DACD), diarrhée associée aux antibiotiques (DAA) et mortalité évitées. L'incertitude a été étudiée à l'aide d'analyses d'amorçage et de sensibilité non paramétriques. RéSULTATS: Le coût moyen (écart type [ÉT]) par patient était de 66 914 (91 098) USD pour les patients randomisés au groupe probiotiques, avec une médiane [écart interquartile (ÉIQ)] de 42 947 USD [22 239 à 76 205]. En comparaison, pour ceux ne recevant pas de probiotiques, le coût moyen (ÉT) par patient était de 62 701 USD (78 676) (médiane [ÉIQ], 41 102 USD [23 170 à 75 140]; coût différentiel, 4213 USD; intervalle de confiance [IC] à 95%, -2269 à 10 708). En matière de rapports coût-efficacité différentiels pour les événements de PAV ou DAA évités, les probiotiques étaient dominés par les soins habituels (plus coûteux, avec une efficacité similaire). Les RCED étaient de 1 473 400 USD par événement de DACD évitée (IC 95 %, non défini) et de 396 764 USD par décès évité (IC 95 %, non défini). Les courbes d'acceptabilité coût-efficacité révèlent que les probiotiques n'étaient pas rentables dans de larges gammes de seuils plausibles de volonté de payer. Les analyses de sensibilité n'ont pas modifié les conclusions. CONCLUSION: Les probiotiques utilisés pour prévenir la PAV chez les patients gravement malades n'étaient pas rentables. Enregistrement de l'étude : www.clinicaltrials.gov (NCT01782755); enregistrée le 4 février 2013.

A scoping review of perceptions from healthcare professionals on antipsychotic prescribing practices in acute care settings.

BACKGROUND: Antipsychotic medications are frequently prescribed in acute care for clinical indications other than primary psychiatric disorders such as delirium. Unfortunately, they are commonly continued at hospital discharge and at follow-ups thereafter. The objective of this scoping review was to characterize antipsychotic medication prescribing practices, to describe healthcare professional perceptions on antipsychotic prescribing and deprescribing practices, and to report on antipsychotic deprescribing strategies within acute care. METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Web of Science databases from inception date to July 3, 2021 for published primary research studies reporting on antipsychotic medication prescribing and deprescribing practices, and perceptions on those practices within acute care. We included all study designs excluding protocols, editorials, opinion pieces, and systematic or scoping reviews. Two reviewers screened and abstracted data independently and in duplicate. The protocol was registered on Open Science Framework prior to data abstraction (10.17605/OSF.IO/W635Z). RESULTS: Of 4528 studies screened, we included 80 studies. Healthcare professionals across all acute care settings (intensive care, inpatient, emergency department) perceived prescribing haloperidol (n = 36/36, 100%) most frequently, while measured prescribing practices reported common quetiapine prescribing (n = 26/36, 76%). Indications for antipsychotic prescribing were delirium (n = 48/69, 70%) and agitation (n = 20/69, 29%). Quetiapine (n = 18/18, 100%) was most frequently prescribed at hospital discharge. Three studies reported in-hospital antipsychotic deprescribing strategies focused on pharmacist-driven deprescribing authority, handoff tools, and educational sessions. CONCLUSIONS: Perceived antipsychotic prescribing practices differed from measured prescribing practices in acute care settings. Few in-hospital deprescribing strategies were described. Ongoing evaluation of antipsychotic deprescribing strategies are needed to evaluate their efficacy and risk.

Health-related quality-of-life and health-utility reporting in critical care.

Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient's functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments.

Impact of Family Presence on Delirium in Critically Ill Patients: A Retrospective Cohort Study.

OBJECTIVE: To assess the effect of family presence on the prevalence and duration of delirium in adults admitted to an ICU. DESIGN: Retrospective cohort study. SETTING: Medical-surgical ICUs in Alberta, AB, Canada. PATIENTS: A population of 25,537 unique patients admitted at least once to an Alberta ICU. METHODS: We obtained electronic health records of consecutive adults (≥ 18 yr) admitted to one of 14 medical-surgical ICU in Alberta, Canada, from January 1, 2014, to December 30, 2018. Family presence was quantified using a validated algorithm and categorized as: 1) physical presence in ICU, 2) telephone call only, and 3) no presence (reference group). Delirium was measured using the Intensive Care Delirium Screening Checklist (ICDSC) and defined as an ICDSC greater than or equal to 4. Multivariable mixed-effects logistic and linear regression were used to evaluate the association between family presence and prevalence (binary) and duration (d) of delirium, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between family presence and delirium prevalence differed according to admission type and admission Glasgow Coma Scale (GCS). Among medical and emergency surgical patients irrespective of admission GCS, physical presence of family was not significantly associated with the prevalence of delirium. In elective surgical patients, physical presence of family was associated with decreased prevalence of delirium in patients with intact Glasgow Coma Scale (GCS = 15; adjusted odds ratio, 0.60; 95% CI, 0.39-0.97; p = 0.02). Physical presence of family (adjusted mean difference [AMD] -1.87 d; 95% CI, -2.01 to -1.81; p < 0.001) and telephone calls (AMD -1.41 d; 95% CI, -1.52 to -1.31; p < 0.001) were associated with decreased duration of delirium in all patients. CONCLUSIONS: The effects of family presence on delirium are complex and dependent on type of visitation, reason for ICU admission, and brain function on ICU admission.

Predicting Abnormal Laboratory Blood Test Results in the Intensive Care Unit Using Novel Features Based on Information Theory and Historical Conditional Probability: Observational Study.

BACKGROUND: Redundancy in laboratory blood tests is common in intensive care units (ICUs), affecting patients' health and increasing health care expenses. Medical communities have made recommendations to order laboratory tests more judiciously. Wise selection can rely on modern data-driven approaches that have been shown to help identify low-yield laboratory blood tests in ICUs. However, although conditional entropy and conditional probability distribution have shown the potential to measure the uncertainty of yielding an abnormal test, no previous studies have adapted these techniques to include them in machine learning models for predicting abnormal laboratory test results. OBJECTIVE: This study aimed to address the limitations of previous reports by adapting conditional entropy and conditional probability to extract features for predicting abnormal laboratory blood test results. METHODS: We used an ICU data set collected across Alberta, Canada, which included 55,689 ICU admissions from 48,672 patients. We investigated the features of conditional entropy and conditional probability by comparing the performances of 2 machine learning approaches for predicting normal and abnormal results for 18 blood laboratory tests. Approach 1 used patients' vitals, age, sex, and admission diagnosis as features. Approach 2 used the same features plus the new conditional entropy-based and conditional probability-based features. Both approaches used 4 different machine learning models (fuzzy model, logistic regression, random forest, and gradient boosting trees) and 10 metrics (sensitivity, specificity, accuracy, precision, negative predictive value [NPV], F1 score, area under the curve [AUC], precision-recall AUC, mean G, and index balanced accuracy) to assess the performance of the approaches. RESULTS: Approach 1 achieved an average AUC of 0.86 for all 18 laboratory tests across the 4 models (sensitivity 78%, specificity 84%, precision 82%, NPV 75%, F1 score 79%, and mean G 81%), whereas approach 2 achieved an average AUC of 0.89 (sensitivity 84%, specificity 84%, precision 83%, NPV 81%, F1 score 83%, and mean G 84%). We found that the inclusion of the new features resulted in significant differences for most of the metrics in favor of approach 2. Sensitivity significantly improved for 8 and 15 laboratory tests across the different classifiers (minimum P<.001 and maximum P=.04). Mean G and index balanced accuracy, which are balanced performance metrics, also improved significantly across the classifiers for 6 to 10 and 6 to 11 laboratory tests. The most relevant feature was the pretest probability feature, which is the probability that a test result was normal when a certain number of consecutive prior tests was already normal. CONCLUSIONS: The findings suggest that conditional entropy-based features and pretest probability improve the capacity to discriminate between normal and abnormal laboratory test results. Detecting the next laboratory test result is an intermediate step toward developing guidelines for reducing overtesting in the ICU.

Non-COVID outcomes associated with the coronavirus disease-2019 (COVID-19) pandemic effects study (COPES): A systematic review and meta-analysis.

BACKGROUND: As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs. METHODS: We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology. RESULTS: Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28-1.50; absolute risk difference: 5% [95% CI: 4-6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty). CONCLUSIONS: There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020201256 (Sept 2, 2020).

Antipsychotic prescribing practices and patient, family member and healthcare professional perceptions of antipsychotic prescribing in acute care settings: a scoping review protocol.

INTRODUCTION: Antipsychotic medications are commonly prescribed off-label in acutely ill patients for non-psychiatric clinical indications such as delirium or insomnia. New prescription initiation of antipsychotics in acute care settings increases the proportion of patients discharged home on antipsychotics without approved clinical indication. Long-term use of antipsychotics is associated with increased risk of sudden cardiac death, falls and cognitive impairment. An understanding of acute care off-label antipsychotic prescribing practices and healthcare professional, patient and family perceptions related to antipsychotic prescribing and deprescribing is necessary to facilitate in-hospital deprescribing initiatives. METHODS AND ANALYSIS: We present the protocol for a scoping review following the methodology proposed by Arksey and O'Malley and the Scoping Review Methods Manual by the Joanna Briggs Institute. We will search five databases including MEDLINE, EMBASE, CINAHL, PsycINFO and Web of Science from inception to 3 July 2021 (ie, planned search date). We will include both peer-reviewed and non-peer-reviewed qualitative and quantitative studies to identify antipsychotic prescribing practices, and to describe healthcare professional, patient and family perceptions towards antipsychotic prescribing and deprescribing in the acute care setting. Protocols, systematic and scoping reviews will be excluded. Two reviewers will calibrate and perform study screening and data abstraction for quantitative and qualitative outcomes of eligible studies. Quantitative outcomes will include study identifiers, demographics and descriptive statistics of antipsychotic prescribing practices. Qualitative synthesis describing perceptions on antipsychotic prescribing practices will include deductive thematic analysis with mapping of themes to the domains of the Theoretical Domains Framework, a 14-domain behaviour and behaviour change framework. ETHICS AND DISSEMINATION: No ethical approval will be required for this study as only data from published studies in which informed consent was obtained by primary investigators will be retrieved and analysed. The results of this scoping review will inform integrated knowledge translation initiatives aimed at in-hospital antipsychotic medication deprescribing.

Monitoring and auditing protocol adherence, data integrity and ethical conduct of a randomized clinical trial: A case study.

PURPOSE: To categorize, quantify and interpret findings documented in feedback letters of monitoring or auditing visits for an investigator-initiated, peer-review funded multicenter randomized trial testing probiotics for critically ill patients. MATERIALS & METHODS: In 37 Canadian centers, monitoring and auditing visits were performed by 3 trained individuals; findings were reported in feedback letters. At trial termination, we performed duplicate content analysis on letters, categorizing observations first into unique findings, followed by 10 pre-determined trial quality management domains. We further classified each observation into a) missing operational records, b) errors in process, and potential threats to c) data integrity, d) patient privacy or e) safety. RESULTS: Across 37 monitoring or auditing visits, 75 unique findings were categorized into 10 domains. Most frequently, observations were in domains of training documentation (180/566 [32%]) and the informed consent process (133/566 [23%]). Most observations were missing operational records (438/566 [77%]) rather than errors in process (128/566 [23%]). Of 75 findings, 13 (62/566 observations [11%]) posed a potential threat to data integrity, 1 (1/566 observation [0.18%]) to patient privacy, and 9 (49/566 observations [8.7%]) to patient safety. CONCLUSIONS: Monitoring and auditing findings predominantly concerned missing documentation with minimal threats to data integrity, patient privacy or safety. TRIAL REGISTRATION: PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial): NCT02462590.