Deborah Joanne Cook

Background: A recent international randomized trial found that the proton pump inhibitor (PPI) pantoprazole significantly reduced the risk of clinically important upper gastrointestinal (GI) bleeding among invasively ventilated patients in the intensive care unit (ICU), with no effect on mortality. Pantoprazole may be of particularly high utility among patients at high-risk of bleeding, such as those receiving renal replacement therapy (RRT) prior to ICU admission. However, given the complex mechanisms by which renal insufficiency may increase bleeding risk, as well as the possible association between PPI use and adverse kidney outcomes, investigating whether kidney failure treated with RRT at baseline modifies the treatment effect of PPIs is clinically relevant. Methods: We have planned a post hoc secondary analysis of the Re-evaluating the Inhibition of Stress Erosions (REVISE) Trial ( NCT03374800 ). The primary objective if this study is to evaluate whether any RRT on study day 1 (e.g., maintenance RRT in the outpatient setting, or RRT initiated in the hospital [intermittent hemodialysis, continuous renal replacement therapy, sustained low efficiency dialysis, or peritoneal dialysis]) modifies the treatment effect of pantoprazole on clinically important upper GI bleeding and 90-day mortality. The secondary objective is to evaluate whether maintenance RRT (intermittent hemodialysis or peritoneal dialysis) in an outpatient setting before the index hospital admission modifies the effect of pantoprazole on clinically important upper GI bleeding and 90-day mortality. Secondary outcomes for both analyses are patient important upper GI bleeding, ICU and hospital mortality. We will perform Cox proportional-hazard analyses, including the RRT exposure of interest, randomized group, and their interaction for each outcome, reporting results as hazards ratios with 95% confidence intervals, and p-values for the interaction term. Conclusion: Results of this study will inform critical care practice, particularly for the care of patients at risk of stress-related GI ulceration in the ICU who have received RRT.

Context: Heartbeat recordings, preserved either as standalone audio recording or integrated into a meaningful song, have been offered as bereavement support by music therapists. Their feasibility and impact within the context of an end-of-life program have not been evaluated.Objective: To assess the feasibility of providing heartbeat recordings within an existing EOL program (the 3 Wishes Program) and explore bereaved families’ experiences and perceptions of this intervention.Methods: Bedside nurses or a music therapist used digital stethoscopes to record dying patients’ heartbeats for families at a two-hospital academic health system. If desired, families collaborated with the music therapist to create personalized songs incorporating the patient’s heartbeat. Quantitative data described implementation, including the number and type of recordings, initiator, completion time, and cost; qualitative analysis of semi-structured interviews explored bereaved family members’ experiences.Results: A total of 166 heartbeat recordings were provided, including 109 standalone recordings and 57 integrated into songs. Nurses recorded 68% of heartbeats, and music therapists recorded 26%. The majority (60%) of the 57 HB songs were completed post-mortem and outside of the hospital. Qualitative analysis of 16 interviews revealed four themes: (1) the creation process was therapeutic; (2) recordings supported grief processing; (3) recordings were cherished as tangible legacy items; and (4) participants strongly recommended offering the intervention to others.Conclusion: Heartbeat recordings and songs can be delivered in an EOL program and are experienced by families as emotionally supportive, meaningful legacy items. These findings support further exploration of heartbeat recordings as a form of bereavement support.

Purpose: To determine the relationship between patient characteristics and treatment fidelity in adult ICU patients enrolled in the CYCLE Pilot randomized controlled trial. Method: We conducted a secondary analysis of a pilot trial in which patients were randomly assigned to in-bed cycling plus usual physiotherapy (PT) or usual PT alone. We calculated protocol fidelity for each patient as the proportion of planned days when the assigned treatment was delivered or did not occur due to medical instability. Using multiple linear regression, we assessed the association of protocol fidelity with admission severity of illness, sex, assigned treatment, baseline comorbidities, and frailty. Results: Sixty-six patients were enrolled in this pilot trial (36 cycling, 30 usual PT) with a median (1st–3rd quartiles) protocol fidelity of 100% (83%–100%), 89% (75%–100%) in cycling and 100% (90%–100%) in usual PT. By regression analysis, assignment to in-bed cycling plus usual PT was associated with a 9.7% (95% CI: –17.8, –1.5) lower protocol fidelity compared to usual PT alone. Conclusions: We found those in the usual PT group had higher protocol fidelity; no other associations were found. This study offers an analytic approach for trialists to assess treatment fidelity for rehabilitation interventions in clinical trials.

Objectives: Observational studies suggest that acid suppression may worsen outcomes among patients infected with SARS-CoV-2. The objectives of this embedded substudy of a randomised controlled trial evaluating pantoprazole in mechanically ventilated patients were to (1) describe the clinical characteristics of critically ill patients with SARS-CoV-2, (2) compare clinical outcomes with a propensity-matched non-infected cohort and (3) assess whether pantoprazole’s treatment effects differed by SARS-CoV-2 infection status. Design: A pre-planned substudy of the re-evaluating the inhibition of stress erosions (REVISE) trial, including a propensity-matched analysis of infected and non-infected patients comparing the effect of pantoprazole between patients with and without SARS-CoV-2. Setting: 68 intensive care units (ICUs) in eight countries. Participants: From July 2019 to October 2023, 4821 eligible participants were enrolled in REVISE whether or not they had SARS-CoV-2 infection. Primary and secondary outcome measures: Participants enrolled in REVISE with SARS-CoV-2 infection had additional data collection, including biomarkers, venous thromboembolism, SARS-CoV-2 therapies and tracheostomy timing. The primary outcomes were clinically important upper gastrointestinal bleeding and 90-day mortality. Secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, patient-important upper GI bleeding, renal replacement therapy, ICU and hospital mortality and duration of mechanical ventilation, ICU and hospital stay. Results: Of the eligible trial cohort, 11.9% (540/4550) had SARS-CoV-2; 532 patients had additional SARS-CoV-2-specific data collection. Of these 532 patients, 87.8% received COVID-19-directed treatments—(dexamethasone 75.2%), 11.7% developed pulmonary embolism and 9.2% developed deep-vein thrombosis. After propensity matching, SARS-CoV-2 infection was not associated with clinically important upper gastrointestinal bleeding (adjusted HR 0.78, 95% CI 0.40 to 1.50) but was associated with significantly higher ICU, hospital and 90-day mortality, as well as longer duration of ventilation and ICU and hospital length of stay. The effect of pantoprazole on clinically important upper GI bleeding and 90-day mortality was consistent regardless of SARS-CoV-2 status. Conclusions: SARS-CoV-2 infection was associated with higher mortality and longer duration of mechanical ventilation, ICU and hospital stays, without an increased risk of clinically important upper gastrointestinal bleeding. Pantoprazole reduced clinically important upper gastrointestinal bleeding without adversely affecting other outcomes. Trial registration number: REVISE trial ( NCT03374800 ), SARS-CoV-2 cohort study ( NCT05715567 ).

OBJECTIVES: Research examining informed consent in critical care studies is limited. The objective of this study was to describe the patterns and predictors of consent. DESIGN: Research coordinators prospectively documented each consent encounter including consent model (a priori or deferred, also known as consent to continue), who requested consent (research coordinator, site investigator, and ICU physician), who provided or declined consent (patient, substitute decision-maker [SDM], and other), the method to obtain consent (in-person or via telephone), and reasons for consent decline, if applicable. Research coordinators retrospectively reported center characteristics. Using multilevel logistic regression, we evaluated the association of consent provision with characteristics of the consent encounter and participating center. SETTING: International randomized trial of stress ulcer prophylaxis for invasively ventilated patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among 5024 patients or SDMs approached for consent, the consent rate was 85.0% (ranging from 27.3% to 100%). In 2638 patients (52.5%), an a priori approach was used, and of these, 696 patients (26.4%) declined. The remaining 2386 participants (47.5%) were enrolled by deferred consent, of whom 58 participants (2.4%) ultimately declined. Among first consent encounters, 80.2% were with SDMs, 19.6% with patients, and 0.2% with others. Higher consent rates were independently associated with the deferred consent model (odds ratio [OR], 16.56; 95% CI, 11.50–23.84), consent encounters involving patients (OR, 2.67; 95% CI, 1.63–4.37), and consent encounters during the COVID-19 pandemic (OR, 2.01; 95% CI, 1.30–3.11) or postpandemic period (OR, 2.26; 95% CI, 1.34–3.80) compared with prepandemic. Consent rates were not associated with center characteristics including ICU size, ICU research experience, or research coordinator experience. CONCLUSIONS: Deferred consent was used as often as a priori consent in this trial. The informed consent rate was associated with the deferred model, consent from patients, and consent encounters during or after the pandemic.

Objective: The objective of this study was to understand experiences of patients, families and clinicians with the Footprints Project - a tool used to counter the unintentional dehumanisation of critically ill patients in the intensive care unit (ICU). Design: Qualitative descriptive study. Setting: 29-bed university-affiliated ICU. Participants: Of 66 participants, 7 were survivors of critical illness, 19 were family members of survivors or decedents and 40 were clinicians representing 10 different professions. Interventions: The Footprints Project uses a written form to record personal details about each patient, then excerpts are transcribed onto a whiteboard in each patient’s room. Patients and family members were invited to participate in semistructured interviews or focus groups after ICU discharge (October 2024–August 2025). Clinicians were invited by email (January 2025–May 2025). Focus groups and interviews were audio-recorded, transcribed and anonymised. Outcome measures: Perspectives and experiences of patients, family members and clinicians. Results: Data collection was primarily in-person for patients and families (17 of 26, 65.4%), and virtual for clinicians (36 of 40, 90.0%). Qualitative content analysis of transcripts revealed three categories related to identity, inclusivity and impact . Footprints was experienced as a tool to highlight personhood by bringing patients into view, individualising conversations and encouraging use of preferred names. Features fostering inclusivity include increasing awareness of vulnerabilities, facilitating culturally-sensitive care and helping to avoid errant assumptions. Patients valued being acknowledged as a person. Families valued recognition of their loved one as an individual. Clinicians found shared humanity through Footprints. Participants identified barriers to consistent use, underscoring implementation challenges; they also shared ideas for more intentional, consistent utilisation. Conclusions: The Footprints Project was viewed as a relational tool, reflecting a patient-facing approach to person-centred, family-partnered care that supports humanism in healthcare. Future work should include structured implementation strategies and assess how Footprints can be sustained and embedded into practice.

Background: In Canada, there is a lack of data relating sociodemographic characteristics to the likelihood of consent and clinical trial participation. Objective: The overall objective of this study is to examine the association of hospital-level sociodemographic variables with a priori informed consent rates for participation in the REVISE trial. Design: This study is a retrospective observational analysis of Canadian sites participating in the international REVISE trial. Methods: Sociodemographic characteristics for 42 hospitals participating in the REVISE trial will be supplemented by national data from the 2021 Canadian Census of Population Profile at the census tract level corresponding to the hospital’s location. Hospital level information for Ontario sites will be derived from the Institute for Clinical Evaluate Sciences (ICES) database. Site clustering will be performed using latent class analysis, a flexible clustering technique that identifies meaningful subgroups based on sociodemographic variables purposively selected from data available through the Statistics Canada 2021 census profile, ICES, and hospital-reported data. Clustering analysis will be performed for all Ontario hospitals with available ICES data, followed by a separate analysis for all Canadian REVISE sites using Statistics Canada data. Concordance in the clustering of REVISE sites will be examined by comparing the assignment of hospitals to the latent classes separately identified using ICES and Statistics Canada data. If there is a high degree of agreement between the two datasets, sociodemographic predictors will be analyzed using the clusters identified through ICES for Ontario sites with the concordant classes based on Statistics Canada data for Canadian sites outsite Ontario. If there is disagreement in cluster assignment between the two datasets, separate analyses of sociodemographic factors will be conducted for Ontario sites using ICES data and for all Canadian sites using the 2021 Census Profile. Multivariate linear regression models will be used to analyze the association between hospital-level characteristics and the likelihood of a priori and deferred consent. Results: Results of this study will generate information about the relationship between informed consent to participate in a low-risk critical care clinical trial using different consent models, and socioeconomic patient characteristics at the hospital site level (e.g., educational attainment, knowledge of official languages, citizenship rates, family income, poverty, rurality and immigration patterns). Conclusions: This study will fill an evidence gap by generating information on the relationship between sociodemographic variables and the likelihood of informed consent to participate in a critical care clinical trial in Canada.

Introduction Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a significant procedural adverse event (AE), occurring in 5–15% of cases and leading to substantial morbidity and mortality. Aggressive prolonged intravenous (IV) fluid regimens have demonstrated efficacy in reducing PEP in clinical trials. However, these regimens typically involve continuous infusion of IV fluids over 8–24 hours following ERCP, making them impractical for outpatient settings. Data on shorter hydration protocols are lacking. The STRIPE study aims to address this gap by evaluating short-term peri-procedural IV fluid regimens as a practical alternative for mitigating PEP. Methods and analysis This proof-of-concept, parallel-arm, randomised controlled trial will evaluate the impact of various short-term IV fluid regimens on post-ERCP serum amylase levels, a surrogate marker for PEP. Participants undergoing ERCP will be randomised into five groups, receiving 500 mL, 1000 mL, 1500 mL, 2000 mL or 2500 mL of IV Ringer’s lactate during the peri-procedural period. Patients, endoscopists and outcome assessors will be blinded to treatment allocation during the peri-procedural period. The primary outcome is the serum amylase level 24 hours post-ERCP. Secondary outcomes include PEP, 30-day AEs and unplanned healthcare encounters including those related to volume overload or cardiovascular AEs, duration of hospitalisation (for inpatients), death within 30 days and other relevant laboratory markers at 24 hours. A total of 505 participants (101 in each arm) will be enrolled to ensure adequate power after accounting for attrition and/or sample loss. Ethics and dissemination This trial was registered on clinicaltrials.gov on 7 February 2024. The study was approved by the University of Calgary Conjoint Health Research Ethics Board (REB23-0625). On study completion, data will be made available on reasonable request to the corresponding author after completion of the study. Study dissemination and knowledge translation is planned via presentations at scholarly meetings, publications in peer-reviewed journals and, ideally, via adoption of results into clinical practice guidelines. Trial registration number NCT06260878.