Showing papers by "Deborah J. Cook published in 2020"

Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis.

Abstract: The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use.

Personalizing Death in the Intensive Care Unit: The 3 Wishes Project

Abstract: This article describes the efforts of a multidisciplinary team to humanize a difficult process by eliciting and fulfilling some simple wishes of dying patients and their families.

Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: an updated systematic review and network meta-analysis of randomized trials.

Abstract: Motivated by a new randomized trial (the PEPTIC trial) that raised the issue of an increase in mortality with proton pump inhibitors (PPIs) relative to histamine-2 receptor antagonists (H2RAs), we updated our prior systematic review and network meta-analysis (NMA) addressing the impact of pharmacological gastrointestinal bleeding prophylaxis in critically ill patients. We searched for randomized controlled trials that examined the efficacy and safety of gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. We performed Bayesian random-effects NMA and conducted analyses using all PEPTIC data as well as a restricted analysis using only PEPTIC data from high compliance centers. We used the GRADE approach to quantify absolute effects and assess the certainty of evidence. Seventy-four trials enrolling 39 569 patients proved eligible. Both PPIs (risk ratio (RR) 1.03, 95% credible interval 0.93 to 1.14, moderate certainty) and H2RAs (RR 0.98, 0.89 to 1.08, moderate certainty) probably have little or no impact on mortality compared with no prophylaxis. There may be no important difference between PPIs and H2RAs on mortality (RR 1.05, 0.97 to 1.14, low certainty), the 95% credible interval of the complete analysis has not excluded an important increase in mortality with PPIs. Both PPIs (RR 0.46, 0.29 to 0.66) and H2RAs (RR 0.67, 0.48 to 0.94) probably reduce clinically important gastrointestinal bleeding; the magnitude of reduction is probably greater in PPIs than H2RAs (RR 0.69, 0.45 to 0.93), and the difference may be important in higher, but not lower bleeding risk patients. PPIs (RR 1.08, 0.88 to 1.45, low certainty) and H2RAs (RR 1.07, 0.85 to 1.37, low certainty) may have no important impact on pneumonia compared with no prophylaxis. This updated NMA confirmed that PPIs and H2RAs are most likely to have a similar effect on mortality compared to each other and compared to no prophylaxis; however, the possibility that PPIs may slightly increase mortality cannot be excluded (low certainty evidence). PPIs and H2RAs probably achieve important reductions in clinically important gastrointestinal bleeding; for higher bleeding risk patients, the greater benefit of PPIs over H2RAs may be important. PPIs or H2RAs may not result in important increases in pneumonia but the certainty of evidence is low.

Compassionate End-of-Life Care: Mixed-Methods Multisite Evaluation of the 3 Wishes Project.

Abstract: The 3 Wishes Project was pioneered in an academic medical center's intensive care unit to promote compassionate end-of-life care by eliciting and fulfilling the wishes of dying patients or their fa...

Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial

Abstract: Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis. LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned. This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis. clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) randomised clinical trial: study protocol.

Abstract: Introduction Bloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied.

Building organizational compassion among teams delivering end-of-life care in the intensive care unit: The 3 Wishes Project.

Abstract: Background:The 3 Wishes Project is a semistructured program that improves the quality of care for patients dying in the intensive care unit by eliciting and implementing wishes. This simple interve...

Frailty and associated prognosis among older emergency department patients with suspected infection: A prospective, observational cohort study.

Abstract: Background Prognosis and disposition among older emergency department (ED) patients with suspected infection remains challenging. Frailty is increasingly recognized as a predictor of poor prognosis among critically ill patients; however, its association with clinical outcomes among older ED patients with suspected infection is unknown. Methods We conducted a multicenter prospective cohort study at two tertiary care EDs. We included older ED patients (≥75 years) with suspected infection. Frailty at baseline (before index illness) was explicitly measured for all patients by the treating physicians using the Clinical Frailty Scale (CFS). We defined frailty as a CFS 5–8. The primary outcome was 30-day mortality. We used multivariable logistic regression to adjust for known confounders. We also compared the prognostic accuracy of frailty with the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) criteria. Results We enrolled 203 patients, of whom 117 (57.6%) were frail. Frail patients were more likely to develop septic shock (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.08–2.51) and more likely to die within 30 days of ED presentation (aOR 2.05; 95% CI, 1.02–5.24). Sensitivity for mortality was highest among the CFS (73.1%; 95% CI, 52.2–88.4), compared with SIRS ≥ 2 (65.4%; 95% CI, 44.3–82.8) or qSOFA ≥ 2 (38.4; 95% CI, 20.2–59.4). Conclusions Frailty is a highly prevalent prognostic factor that can be used to risk-stratify older ED patients with suspected infection. ED clinicians should consider screening for frailty to optimize disposition in this population.

Research Collaboration in Pediatric Critical Care Randomized Controlled Trials: A Social Network Analysis of Coauthorship.

Abstract: Objectives Clinical research is a collaborative enterprise; researchers benefit from the expertise, experience, and resources of their collaborators. We sought to describe the extent and patterns of collaboration among pediatric critical care trialists, and to identify the most influential individuals, centers, and countries. Design Social network analysis of coauthorship. Data sources Publications of pediatric critical care randomized controlled trials (1986-2018). Data extraction We manually extracted the names of all authors and their affiliations. We used productivity (number of randomized controlled trials), influence (number of citations), and four measures of prominence in the social network (degree, betweenness, closeness, and eigenvector centrality) to identify the most influential individuals. Measurements and main results From 415 randomized controlled trials in pediatric critical care, we identified 2,176 trialists from 377 centers in 43 countries. The coauthorship network is highly disconnected and dominated by a single large cluster of trialists publishing 142 (34%) of the randomized controlled trials. However, 119 (29%) of the randomized controlled trials were published by 28 smaller clusters-a median (interquartile range) of 3 (2-4) randomized controlled trials each. The remaining 154 (37%) randomized controlled trials were coauthored by researchers publishing a single randomized controlled trial each. This overall structure has remained constant with the publication of new randomized controlled trials over 33 years. The most influential trialists and centers varied according to the metric we used; only one trialist and three centers ranked in the top 10 for all measures of influence. Thirty-five of the 40 trialists (88%) ranking in the top 10 of any of the measures were from the United States, the United Kingdom, and Canada. Conclusions Pediatric critical care has made considerable progress in the number of trialists and randomized controlled trials, but the research enterprise remains highly clustered and fragmented, particularly geographically. Efforts to further increase the quantity and quality of research in the field should include steps to increase the level and range of collaboration.

A qualitative study of bereaved family members with complicated grief following a death in the intensive care unit.

Abstract: Grief is a normal reaction, and most family members (FMs) experience grief following a death. Typically, grief subsides without any major psychological or medical impairment. Nevertheless, some FMs may experience complicated grief (CG) reactions, with symptoms lasting months or years, and CG is particularly prominent among FMs of those who die in the intensive care unit (ICU). The purpose of this study was to examine how FMs experience grief, particularly CG, to inform future early screening and support programs in the ICU. This was a multicentre qualitative study focusing on semi-structured interviews with FMs who displayed symptoms of CG. Family members of patients who died in the ICU and who had a six-month inventory of CG score > 25 were included. Semi-structured interviews were conducted with FMs post-loss, with follow-up interviews three months after the initial interviews. Major themes identified following thematic analysis from eight participants with CG included 1) ante-mortem experience: the impact of the ICU experience prior to death of a loved on subsequent grief; 2) post-mortem experience: unpredictable post death reactions; 3) coping strategies: techniques used to reduce the severity of grief reactions; 4) sources of support: focusing on resources that the FM draws from for emotional support; and 5) perspectives on future ICU bereavement screening and support programs: advice that FM participants provided for future bereavement support. Bereaved FMs with CG described their experiences with grief, how ICU events influenced their bereavement, their coping strategies and sources of support, and their advice for future bereavement support programs for FMs of deceased ICU patients.

Variability in deceased donor care in Canada: a report of the Canada-DONATE cohort study

Abstract: Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34–35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. Trial registration: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

Probiotics in hospitalized adult patients: a systematic review of economic evaluations

Abstract: Probiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients. We searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence. Of 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency. Probiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy. Trial registration: PROSPERO CRD42019129929; Registered 25 April, 2019.

Principles Guiding Nonpandemic Critical Care Research During a Pandemic.

Abstract: Objectives To describe the importance of critical care clinical research that is not pandemic-focused during pandemic times; outline principles to assist in the prioritization of nonpandemic research during pandemic times; and propose a guiding framework for decisions about whether, when and how to continue nonpandemic research while still honoring the moral and scientific imperative to launch research that is pandemic-focused. Design/data sources Using in-person, email, and videoconference exchanges, we convened an interprofessional clinical research group, conducted a literature review of empirical studies, ethics documents and expert commentaries (2010 to present), and viewed traditional and social media posts (March 2020 to May 2020). Stakeholder consultation involved scientific, ethics, clinical, and administrative leaders. Setting Clinical research in the ICU. Patients Patients with and without coronavirus disease 2019. Interventions None. Measurements and main results While clinical research should be prioritized to advantage patients with coronavirus disease 2019 in order to care for affected patients, it ideally would not unduly disadvantage patients without coronavirus disease 2019. Thus, timely, rigorous, relevant, and ethical clinical research is needed to improve the care and optimize outcomes for both patients with and without coronavirus disease 2019, acknowledging how many studies that are not exclusively focused on coronavirus disease 2019 remain relevant to patients with coronavirus disease 2019. Considerations to continue nonpandemic-focused research include the status of the pandemic, local jurisdictional guidance, capacity and safety of bedside and research personnel, disposition of patients already enrolled in nonpandemic studies, analyzing characteristics of each nonpandemic-focused study, research oversight, and final reporting requirements. Conclusions Deliberation about continuing nonpandemic research should use objective, transparent criteria considering several aspects of the research process such as bedside and research staff safety, infection control, the informed consent model, protocol complexity, data collection, and implementation integrity. Decisions to pause or pursue nonpandemic research should be proportionate, transparent, and revisited as the pandemic abates.

The Efficacy and Safety of In-Intensive Care Unit Leg-Cycle Ergometry in Critically Ill Adults. A Systematic Review and Meta-analysis.

Abstract: Background: Survivors of critical illness may experience physical-function deficits after intensive care unit (ICU) discharge In-ICU cycle ergometry may facilitate early mobilization and decrease

Prediction of RECRUITment In randomized clinical Trials (RECRUIT-IT)-rationale and design for an international collaborative study.

Abstract: Poor recruitment of patients is the predominant reason for early termination of randomized clinical trials (RCTs). Systematic empirical investigations and validation studies of existing recruitment models, however, are lacking. We aim to provide evidence-based guidance on how to predict and monitor recruitment of patients into RCTs. Our specific objectives are the following: (1) to establish a large sample of RCTs (target n = 300) with individual patient recruitment data from a large variety of RCTs, (2) to investigate participant recruitment patterns and study site recruitment patterns and their association with the overall recruitment process, (3) to investigate the validity of a freely available recruitment model, and (4) to develop a user-friendly tool to assist trial investigators in the planning and monitoring of the recruitment process. Eligible RCTs need to have completed the recruitment process, used a parallel group design, and investigated any healthcare intervention where participants had the free choice to participate. To establish the planned sample of RCTs, we will use our contacts to national and international RCT networks, clinical trial units, and individual trial investigators. From included RCTs, we will collect patient-level information (date of randomization), site-level information (date of trial site activation), and trial-level information (target sample size). We will examine recruitment patterns using recruitment trajectories and stratifications by RCT characteristics. We will investigate associations of early recruitment patterns with overall recruitment by correlation and multivariable regression. To examine the validity of a freely available Bayesian prediction model, we will compare model predictions to collected empirical data of included RCTs. Finally, we will user-test any promising tool using qualitative methods for further tool improvement. This research will contribute to a better understanding of participant recruitment to RCTs, which could enhance efficiency and reduce the waste of resources in clinical research with a comprehensive, concerted, international effort.

Expanding the 3 Wishes Project for compassionate end-of-life care: a qualitative evaluation of local adaptations.

Abstract: The 3 Wishes Project (3WP) is an end-of-life program that honors the dignity of dying patients by fostering meaningful connections among patients, families, and clinicians. Since 2013, it has become embedded in the culture of end-of-life care in over 20 ICUs across North America. The purpose of the current study is to describe the variation in implementation of 3WP across sites, in order to ascertain which factors facilitated multicenter implementation, which factors remain consistent across sites, and which may be adapted to suit local needs. Using the methodology of qualitative description, we collected interview and focus group data from 85 clinicians who participated in the successful initiation and sustainment of 3WP in 9 ICUs. We describe the transition between different models of 3WP implementation, from core clinical program to the incorporation of various research activities. We describe various sources of financial and in-kind resources accessed to support the program. Beyond sharing a common goal of improving end-of-life care, sites varied considerably in organizational context, staff complement, and resources. Despite these differences, the program was successfully implemented at each site and eventually evolved from a clinical or research intervention to a general approach to end-of-life care. Key to this success was flexibility and the empowerment of frontline staff to tailor the program to address identified needs with available resources. This adaptability was fueled by cross-pollination of ideas within and outside of each site, resulting in the establishment of a network of like-minded individuals with a shared purpose. The successful initiation and sustainment of 3WP relied on local adaptations to suit organizational needs and resources. The semi-structured nature of the program facilitated these adaptations, encouraged creative and important ways of relating within local clinical cultures, and reinforced the main tenet of the program: meaningful human connection at the end of life. Local adaptations also encouraged a team approach to care, supplementing the typical patient-clinician dyad by explicitly empowering the healthcare team to collectively recognize and respond to the needs of dying patients, families, and each other. NCT04147169 , retrospectively registered with clinicaltrials.gov on October 31, 2019.

Feasibility, Reliability, Responsiveness, and Validity of the Patient-Reported Functional Scale for the Intensive Care Unit: A Pilot Study.

Abstract: Background:Although many performance-based measures assess patients’ physical function in intensive care unit (ICU) survivors, to our knowledge, there are no patient-reported ICU rehabilitation-spe...

Fluid Resuscitation in Sepsis

Abstract: This network meta-analysis of trial data examined the effect of different resuscitative fluids on mortality in patients with sepsis. It showed possible higher mortality with starches than with crys...

Experiences of Bereaved Family Members Receiving Commemorative Paintings: A Qualitative Study.

Abstract: Importance Although family members of patients who die in the intensive care unit commonly experience long-term psychological distress, end-of-life bereavement support programs for such relatives are uncommon. Whether art influences the grief experience of families is largely unexplored. Objective To explore the influence of personalized paintings created to honor deceased critically ill patients on family members' bereavement experience. Design, setting, and participants A qualitative descriptive analysis was conducted of semistructured interviews of grieving relatives who received a painting after the death of their loved one. The deceased patients were from a 21-bed medical-surgical intensive care unit. Eleven families were invited to receive a painting, of whom 1 family declined. A total of 22 family members of 10 patients who died in the intensive care unit were interviewed in the study between July 11, 2017, and May 19, 2019. Interventions Patients were enrolled in an end-of-life care program that elicits and implements wishes of patients and their families to bring peace during the dying process. Selected families of 10 decedents were invited to receive a painting to honor their loved one 1 to 10 months after the patient's death. Using details about the patient's life story, the artist created individualized paintings to commemorate each patient. Main outcomes and measures The experiences of family members receiving a personalized painting and its reported influence on their grieving experience. Results The family members of 10 decedents (mean [SD] age, 60 [14] years; 5 women [50%]; 8 White patients [80%]) were interviewed. The central theme of art to facilitate healing was illustrated through the following domains: the cocreation process, painting narratives, postmortem connections, and legacy. The process of cocreating the paintings with the artist and family members involved reminiscing, storytelling, and creativity. Family members emphasized the role of art to facilitate healing, exemplified through connections with images portrayed that deeply resonated with memories of their loved one. Participants indicated that the paintings validated that the patient was remembered, helped families feel less alone during a time of grief, honored the loved one's life, and enhanced connections between family members and clinicians. Conclusions and relevance This qualitative study's findings suggest that the creation of personalized paintings commemorating the lives of patients may help foster legacy and postmortem connections with clinicians and may help family members in their healing process.

A pilot randomized controlled trial of 7 versus 14 days of antibiotic treatment for bloodstream infection on non-intensive care versus intensive care wards

Abstract: The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards. We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients. A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1–4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001). Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients. It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results. Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.

Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol.

Abstract: Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU) Probiotics are defined as live microorganisms that may confer health benefits when ingested Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile-associated diarrhoea (CDAD) PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients E-PROSPECT will be performed from the public healthcare payer's perspective over a time horizon from ICU admission to hospital dischargeWe will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital 'hoteling' costs not otherwise encompassed The primary outcome is the incremental cost per VAP prevented between the two treatment groups Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019 Informed consent was obtained from the patient or substitute decision-maker in PROSPECT The findings of this study will be published in peer-reviewed journals Trial registration number NCT01782755; Pre-results

Using bioimpedance analysis to assess intensive care unit patients with sepsis in the post-resuscitation period: a prospective multicentre observational study.

Abstract: Clinicians lack well-validated, non-invasive, objective tools to guide volume management in the post-resuscitative period. Bioimpedance analysis (BIA) represents a novel method for guiding fluid management. We studied the relationship of BIA vector length (VL), an indicator of volume status, to the need for mechanical ventilation in patients with sepsis. This is a multicentre prospective observational study at four Canadian ICUs. We examined adult patients admitted to the ICU within 72 hr of a sepsis diagnosis. Patients underwent daily BIA measurements for 30 days, until discharge from the ICU, or until death. Our primary outcome was the ongoing need for invasive mechanical ventilation, and we examined the association with VL using a generalized estimating equation. Our secondary analyses were targeted to determine an association between VL and other measures of volume status and acute kidney injury (AKI). We enrolled 159 patients from four centres over 27 months. The mean (standard deviation [SD]) age was 64 (15) yr with a mean (SD) APACHE (acute physiology, age, chronic health evaluation) II score of 25 (10); 57% (n = 91) were male. A 50-unit (ohm·m) increase in VL over any time period was associated with a 30% decrease in the probability of requiring invasive mechanical ventilation (P < 0.03). Volume expansion, indicated by a shorter VL, correlated with higher edema scores (r = − 0.31; P < 0.001) and higher net 24-hr fluid balance (r = − 0.27, P < 0.001). Patients with AKI had a shorter overall VL (r = − 0.23; P = 0.003). An increase in VL over time is associated with a decrease in probability of requiring invasive mechanical ventilation. Vector length correlates with other commonly used volume assessment methods in post-resuscitation patients with sepsis.

Critical care providers’ support of families in bereavement: a mixed-methods study

Abstract: When people die in intensive care units (ICUs), as many as half of their family members may experience a severe grief reaction. While families report a need for bereavement support, most ICUs do not routinely follow-up with family members. Clinicians are typically involved in supporting families during death and dying, yet little is known about how they work with families in bereavement. Our goal was to explore how clinicians support bereaved families, identify factors that facilitate and hinder support, and understand their interest and needs for follow-up. Mixed-methods study of nurses and physicians working in one of nine adult medical-surgical ICUs in academic hospitals across Canada. Qualitative interviews followed quantitative surveys to reflect, expand, and explain the quantitative results. Both physicians and nurses perceived that they provided empathetic support to bereaved families. Emotional engagement was a crucial element of support, but clinicians were not always able to engage with families because of their roles, responsibilities, experiences, or unit resources. Another important factor that could facilitate or challenge engagement was the degree to which families accepted death. Clinicians were interested in participating in a follow-up bereavement program, but their participation was contingent on time, training, and the ability to manage their own emotions related to death and bereavement in the ICU. Multiple opportunities were identified to enhance current bereavement support for families, including the desire of ICU clinicians for formal follow-up programs. Many psychological, sociocultural, and structural factors would need to be considered in program design.

The effect of COVID-19 on critical care research: A prospective longitudinal multinational survey

Abstract: Importance The COVID-19 pandemic has increased the need for high-quality evidence in critical care, while also increasing the barriers to conducting the research needed to produce such evidence. Objective To determine the effect of the first wave of the COVID-19 pandemic on critical care clinical research. Design Monthly electronic survey (March - August 2020). Setting Adult or pediatric intensive care units (ICUs) from any country participating in at least one research study before the COVID-19 pandemic. Participants We recruited one researcher or research coordinator per center, identified via established research networks. Intervention(s) None Main Outcome(s) and Measure(s) Primary: Suspending recruitment in clinical research; Secondary: impact of specific factors on research conduct (5-point scales from no effect to very large effect). We assessed the association between research continuity and month, presence of hospitalized patients with COVID-19, and population (pediatric vs. adult ICU) using mixed-effects logistic regression. Results 126 centers (56% pediatric) from 23 countries participated. 95 (75%) of centers suspended recruitment in at least some studies and 37 (29%) suspended recruitment in all studies on at least one month. The proportion of centers reporting recruitment in all studies increased over time (OR per month 1.3, 95% CI 1.1 to 1.5, p = 0.007), controlling for hospitalized patients with COVID-19 and type of ICU (pediatric vs. other). The five factors most frequently identified as having a large or very large effect on clinical research were: local prioritization of COVID-19 specific research (68, 54%), infection control policies limiting access to patients with COVID-19 (61, 49%), infection control policies limiting access to the ICU (52, 41.6%), increased workload of clinical staff (38, 30%), and safety concerns of research staff (36, 29%). Conclusions and Relevance Decisions to pause or pursue clinical research varied across centers. Research activity increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles to safely sustain research during this and future pandemic waves are urgently needed. Key Points Question What was the effect of the COVID-19 pandemic on research in 126 adult and pediatric intensive care units (ICUs) between March and August 2020? Findings 95 (75%) centers suspended recruitment in at least some studies. Decisions to continue recruitment increased over time (OR per month 1.3, 95% CI 1.1 to 1.5, p = 0.007), controlling for ICU type and the presence of patients with COVID-19. Meaning Research activity varied across centers and increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles to safely sustain research during this and future pandemic waves are urgently needed.

Review: Albumin does not reduce death in critically ill patients with hypovolemia, burns, or hypoalbuminemia

Abstract: Source Citation Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ. 1998 Jul 25; 317:235-40. ...

Family and Clinician Experiences of Sympathy Cards in the 3 Wishes Project.

Abstract: Background A recent randomized trial of bereaved family members of patients who died in an intensive care unit identified symptoms of depression and posttraumatic stress in recipients of semistructured condolence letters. Objectives To explore family member and clinician experiences with receiving or sending handwritten sympathy cards upon the death of patients involved in a personalized end-of-life intervention, the 3 Wishes Project. Methods Interviews and focus groups were held with 171 family members and 222 clinicians at 4 centers to discuss their experiences with the 3 Wishes Project. Interview transcripts were searched to identify participants who discussed sympathy cards. Data related to sympathy cards were independently coded by 2 investigators through conventional content analysis. Results Sympathy cards were discussed during 32 interviews (by 25 family members of 21 patients and by 11 clinicians) and 2 focus groups (8 other clinicians). Family members reported that personalized sympathy cards were a welcome surprise; they experienced them as a heartfelt act of compassion. Clinicians viewed cards as an opportunity to express shared humanity with families, reminding them that they and their loved one were not forgotten. Signing cards allowed clinicians to reminisce individually and collectively with colleagues. Family members and clinicians experienced sympathy cards as a meaningful continuation of care after a patient's death. Conclusions Inviting clinicians who cared for deceased patients to offer personalized, handwritten condolences to bereaved family members may cultivate sincere and individualized expressions of sympathy that bereaved families appreciate after the death of patients involved in the 3 Wishes Project.