RNA. Introduction.

Two scientists walk into a bar. After a pint and an exchange of pleasantries, one says to the other, "Where do you come from? Scientifically, I mean." The queried scientist responds, "Out of the RNA world." "Don't we all," the asker responds chuckling. Fifteen years ago, the joke would have been made with a nod to the notion that life arose from an RNA-based precursor, the so-called "RNA world." Yet had this conversation happened last week, the scientists would also be grinning in appreciation of the extent to which contemporary cellular biology is steeped in all things RNA. Ours is truly an RNA world.In this year's special review issue, the Cell editorial team has brought together articles focused on RNA in the modern world, providing perspectives on classical and emerging areas of inquiry. We extend our thanks to the many distinguished experts who contributed their time and effort as authors and reviewers to make the issue informative, thought-provoking, and timely. We hope that this collection of articles, written as we stand on the verge of a new wave of RNA biology, edifies and inspires by revealing the inner workings of these versatile molecules and by highlighting the next key questions that need to be addressed as we strive to understand the full functional scope of RNA in cells.

Family Member Experiences in Intensive Care Units Care: Insights From a Family Involvement Tool Implementation Trial.

Family involvement is widely considered an important part of patient care in the intensive care unit. From professional health care organizations, government, and hospital associations, there has been a cultural shift toward family presence as part of a wider commitment to patient-centered care. At the same time, the meaning and impact of family involvement in the intensive care unit setting remain opaque and under-studied. This study employed an ethnographic approach to better understand family involvement in practice and from the perspective of health care professionals and family members by studying an implementation trial of a family involvement tool in two intensive care units over 2 years. The findings revealed that an expanded and self-defined role for family members as carers in the intensive care unit challenged the current configuration of the nurse patient/family relationship and that family members were aware of these dynamics. While the intensive care unit implementation teams were both motivated to implement a novel way of facilitating family involvement, the processual, organizational, and contextual factors in the intensive care units largely determined the possibilities of its application. This suggests that interventions should address the specific context in which they are employed.

Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury.

BACKGROUND: Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. METHODS: We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days. RESULTS: Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001). CONCLUSIONS: Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).

Evidence-Based Approaches to Mitigate Workplace Violence From Patients and Visitors in Emergency Departments: A Rapid Review.

INTRODUCTION: This is a rapid review of the published evidence on the effectiveness of interventions for mitigating workplace violence against staff in hospital emergency departments. Focused on the specific needs of an urban emergency department in Canada, this project sought to address the question, "What interventions have evidence regarding effectiveness for addressing workplace patient/visitor violence toward staff in the emergency department?" METHODS: Following Cochrane Rapid Review methods, 5 electronic databases (MEDLINE via PubMed, Cochrane CENTRAL, Embase, PsycINFO, CINAHL) and Google Scholar were searched in April 2022 for intervention studies to reduce or mitigate workplace violence against staff in hospital emergency departments. Critical appraisal was conducted using Joanna Briggs Institute tools. Key study findings were synthesized narratively. RESULTS: Twenty-four studies (21 individual studies, 3 reviews) were included in this rapid review. A variety of strategies for reducing and mitigating workplace violence were identified and categorized as single or multicomponent interventions. Although most studies reported positive outcomes on workplace violence, the articles offered limited descriptions of the interventions and/or lacked robust data to demonstrate effectiveness. Insights from across the studies offer knowledge users information to support the development of comprehensive strategies to reduce workplace violence. DISCUSSION: Despite a large body of literature on workplace violence, there is little guidance on effective strategies to mitigate workplace violence in emergency departments. Evidence suggests that multicomponent approaches targeting staff, patients/visitors, and the emergency department environment are essential to addressing and mitigating workplace violence. More research is needed that provides robust evidence on effective violence prevention interventions.

Reverse Triggering Dyssynchrony 24 h after Initiation of Mechanical Ventilation.

BACKGROUND: Reverse triggering is a delayed asynchronous contraction of the diaphragm triggered by passive insufflation by the ventilator in sedated mechanically ventilated patients. The incidence of reverse triggering is unknown. This study aimed at determining the incidence of reverse triggering in critically ill patients under controlled ventilation. METHODS: In this ancillary study, patients were continuously monitored with a catheter measuring the electrical activity of the diaphragm. A method for automatic detection of reverse triggering using electrical activity of the diaphragm was developed in a derivation sample and validated in a subsequent sample. The authors assessed the predictive value of the software. In 39 recently intubated patients under assist-control ventilation, a 1-h recording obtained 24 h after intubation was used to determine the primary outcome of the study. The authors also compared patients' demographics, sedation depth, ventilation settings, and time to transition to assisted ventilation or extubation according to the median rate of reverse triggering. RESULTS: The positive and negative predictive value of the software for detecting reverse triggering were 0.74 (95% CI, 0.67 to 0.81) and 0.97 (95% CI, 0.96 to 0.98). Using a threshold of 1 µV of electrical activity to define diaphragm activation, median reverse triggering rate was 8% (range, 0.1 to 75), with 44% (17 of 39) of patients having greater than or equal to 10% of breaths with reverse triggering. Using a threshold of 3 µV, 26% (10 of 39) of patients had greater than or equal to 10% reverse triggering. Patients with more reverse triggering were more likely to progress to an assisted mode or extubation within the following 24 h (12 of 39 [68%]) vs. 7 of 20 [35%]; P = 0.039). CONCLUSIONS: Reverse triggering detection based on electrical activity of the diaphragm suggests that this asynchrony is highly prevalent at 24 h after intubation under assist-control ventilation. Reverse triggering seems to occur during the transition phase between deep sedation and the onset of patient triggering.

Organ Donation at the End of Life: Experiences From the 3 Wishes Project.

PURPOSE: The 3 Wishes Project (3WP) promotes holistic end-of-life care in the intensive care unit (ICU) to honor dying patients, support families, and encourage clinician compassion. Organ donation is a wish that is sometimes made by, or on behalf of, critically ill patients. Our objective was to describe the interface between the 3WP and organ donation as experienced by families, clinicians, and organ donation coordinators. METHODS: In a multicenter evaluation of the 3WP in 4 Canadian ICUs, we conducted a thematic analysis of transcripts from interviews and focus groups with clinicians, organ donation coordinators, and families of dying or died patients for whom donation was considered. RESULTS: We analyzed transcripts from 26 interviews and 2 focus groups with 18 family members, 17 clinicians, and 6 organ donation coordinators. The central theme describes the mutual goals of the 3WP and organ donation-emphasizing personhood and agency across the temporal continuum of care. During family decision-making, conversations encouraged by the 3WP can facilitate preliminary discussions about donation. During preparation for donation, memory-making activities supported by the 3WP redirect focus toward personhood. During postmortem family care, the 3WP supports families, including when donation is unsuccessful, and highlights aspirational pursuits of donation while encouraging reflections on other fulfilled wishes. CONCLUSIONS: Organ donation and the 3WP provide complementary opportunities to engage in value-based conversations during the dying process. The shared values of these programs may help to incorporate organ donation and death into a person's life narrative and incorporate new life into a person's death narrative.

Interventions to enable communication for adult patients requiring an artificial airway with or without mechanical ventilator support.

BACKGROUND: Inability to communicate in a manner that can be understood causes extreme distress for people requiring an artificial airway and has implications for care quality and patient safety. Options for aided communication include non-vocal, speech-generating, and voice-enabling aids. OBJECTIVES: To assess effectiveness of communication aids for people requiring an artificial airway (endotracheal or tracheostomy tube), defined as the proportion of people able to: use a non-vocal communication aid to communicate at least one symptom, need, or preference; or use a voice-enabling communication aid to phonate to produce at least one intelligible word. To assess time to communication/phonation; perceptions of communication; communication quality/success; quality of life; psychological distress; length of stay and costs; and adverse events. SEARCH METHODS: We searched the Cochrane Library (Wiley version), MEDLINE (OvidSP), Embase (OvidSP), three other databases, and grey literature from inception to 30 July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs, controlled non-randomised parallel group, and before-after studies evaluating communication aids used in adults with an artificial airway. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two review authors independently performed data extraction and assessment of risk of bias. MAIN RESULTS: We included 11 studies (1931 participants) conducted in intensive care units (ICUs). Eight evaluated non-vocal communication aids and three voice-enabling aids. Usual care was the comparator for all. For six studies, this comprised no aid; usual care in the remaining five studies comprised use of various communication aids. Overall, our confidence in results regarding effectiveness of communication interventions was very low due to imprecision, measurement heterogeneity, inconsistency in results, and most studies at high or unclear risk of bias across multiple domains. No non-vocal aid studies reported our primary outcome. We are uncertain of the effects of early use of a voice-enabling aid compared to routine use on ability to phonate at least one intelligible word (risk ratio (RR) 3.03, 95% confidence interval (CI) 0.18 to 50.08; 2 studies; very low-certainty evidence). Compared to usual care without aids, we are uncertain about effects of a non-vocal aid (communication board) on patient satisfaction (standardised mean difference (SMD) 2.92, 95% CI 1.52 to 4.33; 4 studies; very low-certainty evidence). No studies of non-vocal aids reported quality of life. Low-certainty evidence from two studies suggests early use of a voice-enabling aid may have no effect on quality of life (MD 2.27, 95% CI -7.21 to 11.75). Conceptual differences in measures of psychological distress precluded data pooling; however, intervention arm participants reported less distress suggesting there might be benefit, but our certainty in the evidence is very low. Low-certainty evidence suggest voice-enabling aids have little or no effect on ICU length of stay; we were unable to determine effects of non-vocal aids. Three studies reported different adverse events (physical restraint use, bleeding following tracheostomy, and respiratory parameters indicating respiratory decompensation). Adverse event rates were similar between arms in all three studies. However, uncertainty remains as to any harm associated with communication aids. AUTHORS' CONCLUSIONS: Due to a lack of high-quality studies, imprecision, inconsistency of results, and measurement heterogeneity,  the evidence provides insufficient information to guide practice as to which communication aid is more appropriate and when to use them. Understanding effectiveness of communication aids would benefit from development of a core outcome measurement set.

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

Background: The 3 Wishes Project (3WP) is an end-of-life program that aims to honor the dignity of dying patients by creating meaningful patient- and family-centered memories while promoting humanistic interprofessional care. Objective: To determine whether this palliative intervention could be successfully implemented-defined as demonstrating value, transferability, affordability, and sustainability-beyond the intensive care unit in which it was created. Design: Mixed-methods formative program evaluation. (ClinicalTrials.gov: NCT04147169). Setting: 4 North American intensive care units. Participants: Dying patients, their families, clinicians, hospital managers, and administrators. Intervention: Wishes from dying patients, family members, and clinicians were elicited and implemented. Measurements: Patient characteristics and processes of care; the number, type, and cost of each wish; and semistructured interviews and focus groups with family members, clinicians, and managers. Results: A total of 730 patients were enrolled, and 3407 wishes were elicited. Qualitative data were gathered from 75 family members, 72 clinicians, and 20 managers or hospital administrators. Value included intentional comforting of families as they honored the lives and legacies of their loved ones while inspiring compassionate clinical care. Factors promoting transferability included family appreciation and a collaborative intensive care unit culture committed to dignity-conserving end-of-life care. Staff participation evolved from passive support to professional agency. Program initiation required minimal investment for reusable materials; thereafter, the mean cost was $5.19 (SD, $17.14) per wish. Sustainability was demonstrated by the continuation of 3WP at each site after study completion. Limitation: This descriptive formative evaluation describes tertiary care center-specific experiences rather than aiming for generalizability to all jurisdictions. Conclusion: The 3WP is a transferrable, affordable, and sustainable program that provides value to dying patients, their families, clinicians, and institutions. Primary Funding Source: Greenwall Foundation.

One-Year Readmission Following Undifferentiated Acute Hypercapnic Respiratory Failure.

Patients with acute hypercapnic respiratory failure (AHRF) often require hospitalization and respiratory support. Early identification of patients at risk of readmission would be helpful. We evaluated 1-y readmission and mortality rates of patients admitted for undifferentiated AHRF and identified the impact of initial severity on clinically important outcomes. We retrospectively analyzed patients who presented with AHRF to the emergency department of St Michael's Hospital in 2017. We collected data about patients' characteristics, hospital admission, readmission and mortality one year after the index admission. We analyzed predictors of readmission and mortality and conducted a survival analysis comparing patients who did and did not receive ventilatory support. A cohort of 212 patients with AHRF who survived their hospital admission were analyzed. At one year, 150 patients (70.8%) were readmitted and 19 (9%) had died. Main diagnoses included chronic obstructive pulmonary disease (60%), congestive heart failure (36%), asthma (22%) and obesity (19%), and these categories of patients had similar 1 y readmission rates. One third had more than one coexisting chronic illness. Although comorbidities were more frequent in readmitted patients, only a history of previous hospital admissions remained associated with 1 y readmission and mortality in multivariate analysis. Need for ventilatory support at admission was not associated with higher 1 y probability of readmission or death. Undifferentiated AHRF is the presentation of multiple chronic illnesses. Patients who survive one episode of AHRF and with previous history of admission have the highest risk of readmission and death regardless of whether they receive ventilatory support during index admission.

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

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 intervention honors the legacy of patients and eases family grief, forging human connections between family members and clinicians. AIM: To examine how the 3 Wishes Project enables collective patterns of compassion between patients, families, clinicians, and managerial leaders in the intensive care unit. DESIGN: Using a qualitative descriptive approach, interviews and focus groups were used to collect data from family members of dying patients, clinicians, and institutional leaders. Unconstrained directed qualitative content analysis was performed using Organizational Compassion as the analytic framework. SETTING/PARTICIPANTS: Four North American intensive care units, participants were 74 family members of dying patients, 72 frontline clinicians, and 20 managerial leaders. RESULTS: The policies and processes of the 3 Wishes Project exemplify organizational compassion by supporting individuals in the intensive care unit to collectively notice, feel, and respond to suffering. As an intervention that enables and empowers clinicians to engage in acts of kindness to enhance end-of-life care, the 3 Wishes Project is particularly well situated to encourage collective responses to suffering and promote compassion between patients, family members, and clinicians. CONCLUSIONS: Examining the 3 Wishes Project through the lens of organizational compassion reveals the potential of this program to cultivate the capacity for people to collectively notice, feel, and respond to suffering. Our data document multidirectional demonstrations of compassion between clinicians and family members, forging the type of human connections that may foster resilience.

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

PURPOSE: 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. METHODS: 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. 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. CONCLUSIONS: 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.

RéSUMé: OBJECTIF: Lorsque des personnes décèdent dans une unité de soins intensifs (USI), jusqu'à la moitié des membres de leur famille pourraient souffrir d'une réaction émotionnelle grave. Bien que les familles rapportent le besoin d'un soutien en cas de deuil, la plupart des USI ne font pas un suivi de routine avec les membres de la famille. Les cliniciens sont traditionnellement impliqués dans le soutien aux familles pendant la mort et le décès, mais nous ne connaissons que peu de choses concernant leur travail avec les familles en deuil. Notre objectif était d'explorer la façon dont les cliniciens viennent en soutien aux familles en deuil, d'identifier les facteurs qui facilitent ou entravent le soutien, et de comprendre leur intérêt et leurs besoins en matière de suivi. MéTHODE: Nous avons réalisé une étude par méthodes mixtes auprès du personnel infirmier et des médecins travaillant dans l'une de neuf USI médico-chirurgicales pour adultes dans des hôpitaux universitaires du Canada. Des entretiens qualitatifs suivaient des sondages quantitatifs afin de refléter, approfondir et expliquer les résultats quantitatifs. RéSULTATS: Selon leur perception, les médecins et le personnel infirmier fournissent un soutien empathique aux familles en deuil. L'implication émotionnelle a été identifiée comme étant un élément crucial du soutien, mais les cliniciens ne sont pas toujours capables de s'impliquer auprès des familles en raison de leurs rôles, de leurs responsabilités, de leurs expériences ou des ressources de l'unité. Un autre facteur important qui pourrait faciliter ou au contraire entraver leur implication est la mesure dans laquelle les familles acceptent la mort. Les cliniciens seraient intéressés à participer à un programme de suivi de deuil, mais leur participation dépend de leur temps, de leur formation et de leur capacité à gérer leurs propres émotions liées à la mort et au deuil à l'USI. CONCLUSION: De nombreuses cibles ont été identifiées pour améliorer le soutien actuel aux familles en deuil, y compris le désir des cliniciens de l'USI de disposer de programmes formels de suivi. Il faudra toutefois tenir compte de nombreux facteurs psychologiques, socioculturels et structurels dans la conception de tels programmes.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

RéSUMé: OBJECTIF: Le deuil est une réaction normale et la plupart des membres d'une famille l'éprouvent après un décès. Habituellement, le deuil décroit sans laisser de troubles psychologiques ou médicaux majeurs. Néanmoins, certains membres d'une famille peuvent présenter des réactions de deuil compliquées, avec des symptômes durant des mois ou des années et ce deuil compliqué est particulièrement visible lorsqu'un membre de la famille est décédé dans une unité de soins intensifs (USI). Cette étude avait pour objectif d'examiner comment les membres d'une famille vivent un deuil, en particulier un deuil compliqué, pour renseigner de futurs programmes de dépistage précoce et de soutien en USI. MéTHODES: Il s'est agi d'une étude qualitative multicentrique utilisant principalement des entretiens semi-structurés avec des membres de familles qui présentaient des symptômes de deuil compliqué. Des membres de la famille de patients décédés en USI qui dans les derniers 6 mois avaient un score > 25 au questionnaire de deuil compliqué ont été inclus. Les entretiens semi-structurés ont été menés après le décès avec des membres de la famille et des entretiens de suivi ont eu lieu trois mois après l'entretien initial. RéSULTATS: Les principaux thèmes identifiés après une analyse thématique de huit participants ayant un deuil compliqué ont inclus : 1) le vécu avant le décès : l'impact de l'expérience de l'USI avant le décès d'un être cher sur le deuil qui a suivi; 2) le vécu après le décès : les réactions imprévisibles après le décès; 3) les stratégies de réponse face au stress : Les techniques utilisées pour réduire les réactions de deuil; 4) les sources de soutien : en se concentrant sur les ressources que le membre de la famille utilise pour un soutien émotionnel; et 5) le point de vue sur de futurs programmes de dépistage et de soutien en USI : les conseils que les membres participants des familles ont donnés pour un futur soutien du deuil. CONCLUSION: Les membres de familles endeuillées présentant un deuil compliqué ont décrit leur vécu du deuil, comment les événements vécus en USI l'ont influencé, leurs stratégies de réponse et la source des soutiens utilisés, ainsi que leurs conseils pour de futurs programmes de soutien du deuil destinés aux familles de patients décédés en USI.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: NCT04147169 , retrospectively registered with clinicaltrials.gov on October 31, 2019.

Gender Parity in Critical Care Medicine.

Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. These documents inform and shape patient care around the world. In this Perspective we discuss the importance of diversity on guideline panels, the disproportionately low representation of women on critical care guideline panels, and existing initiatives to increase the representation of women in corporations, universities, and government. We propose five strategies to ensure gender parity within critical care medicine.

Nurse Research Experiences and Attitudes Toward the Conduct of Intensive Care Research: A Questionnaire Study.

OBJECTIVE: To characterize ICU nurses' research experience, work environments, and attitudes toward clinical research in critically ill adults and children. DESIGN: Cross-sectional survey. SETTING: Eight (seven adult and one pediatric) academic ICUs affiliated with the Canadian Critical Care Trials Group. PARTICIPANTS: Four hundred eighty-two ICU nurses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Response rate was 56%. Most participants had over 6 years of ICU experience (61%) and held a baccalaureate nursing degree (57%). Most participants (63%) had provided care for patients receiving research study procedures more than five times in the past 12 months and agreed that research leads to improved care for the critically ill (78%) and eligible patients should be approached for research participation (78%). Few perceived practicalities of nursing care are considered in study design (20%); 41% agreed that research studies increases nursing workload. Few participants reported receiving adequate information about study progress (24%) or findings (26%). Principal factor analysis identified three factors each in the environmental and attitudinal domains. Linear regression models demonstrated that positive relationships between researchers and clinicians were associated with favorable perceptions of research impact on nursing care (p < 0.001), ICU research acceptability (p < 0.001), and nursing engagement in research (p < 0.05). Nurses with more formal education reported more favorable attitudes toward nursing engagement in research (p < 0.01) and research acceptability (p < 0.01). Lack of experience in study protocol development and/or data analysis was associated with less favorable attitudes about nursing engagement in research (p < 0.01) and impact of research on nursing care (p < 0.01). CONCLUSION: In these research-intensive ICUs, nurses frequently care for research participants and believe ICU research is important. Inclusion of nurses in study protocol development, improved communication of study progress and findings, and investigation of research-related nursing workload are warranted. Such interventions will support intervention fidelity and data reliability during study conduct and translation of evidence into practice on study completion.

The Postcardiac Arrest Consult Team: Impact on Hospital Care Processes for Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVE: To evaluate whether a Post-Arrest Consult Team improved care and outcomes for patients with out-of-hospital cardiac arrest. DESIGN: Prospective cohort study of Post-Arrest Consult Team implementation at two hospitals, with concurrent controls from 27 others. SETTING: Twenty-nine hospitals within the Strategies for Post-Arrest Care Network of Southern Ontario, Canada. PATIENTS: We included comatose adult nontraumatic out-of-hospital cardiac arrest patients surviving more than or equal to 6 hours after emergency department arrival who had no contraindications to targeted temperature management. INTERVENTION: The Post-Arrest Consult Team was an advisory consult service to improve 1) targeted temperature management, 2) assessment for percutaneous coronary intervention, 3) electrophysiology assessment, and 4) appropriately delayed neuroprognostication. MEASUREMENTS AND MAIN RESULTS: We used generalized linear mixed models to explore the association between Post-Arrest Consult Team implementation and performance of targeted processes. We included 1,006 patients. The Post-Arrest Consult Team was associated with a significant reduction over time in rates of withdrawal of life-sustaining therapy within 72 hours of emergency department arrival on the basis of predictions of poor neurologic prognosis (ratio of odds ratios, 0.13; 95% CI, 0.02-0.98). Post-Arrest Consult Team was not associated with improved successful targeted temperature management (ratio of odds ratios, 0.91; 95% CI, 0.31-2.65), undergoing angiography (ratio of odds ratios, 1.91; 95% CI, 0.17-21.04), receiving electrophysiology consultation (ratio of odds ratios, 0.93; 95% CI, 0.11-8.16), or functional survival (ratio of odds ratios, 0.75; 95% CI, 0.19-2.94). CONCLUSIONS: Implementation of a Post-Arrest Consult Team reduced premature withdrawal of life-sustaining therapy but did not improve rates of successful targeted temperature management, coronary angiography, formal electrophysiology assessments, or functional survival for comatose patients after out-of-hospital cardiac arrest.

A National Survey of Critical Care Physicians' Knowledge, Attitudes, and Perceptions of Antimicrobial Stewardship Programs.

OBJECTIVE: Antimicrobial stewardship is a process designed to optimize antimicrobial therapy by ensuring patients get the right antimicrobials at the right dose and at the right time. Antimicrobial stewardship programs (ASPs) are increasingly being implemented in health care institutions, are required by some accreditation bodies, and have the potential for maximum impact in intensive care units (ICUs). We administered a survey to critical care physicians across Canada to better understand their knowledge, attitudes, and perceptions on the utility of ASPs in improving patient care. DESIGN, SETTING, AND PATIENTS: We distributed a Web-based survey to physicians who attend in Canadian ICUs. Respondents were identified through the membership lists of multiple critical care organizations. Content validity, utility, clarity, and test-retest reliability were evaluated prior to distribution. Survey items assessed ASP knowledge, attitudes, and experiences. Attitudes toward ASPs were assessed on a 5-point Likert-type scale. MEASUREMENTS AND MAIN RESULTS: The survey was completed by 185 physicians, with a response rate of 29% (n = 185/634) for all physicians contacted. A majority (74%) of respondents reported that there was at least 1 component of an ASP at their institution. Most (86%) respondents agreed or strongly agreed that the patients in their ICU benefit from an ASP, with 81% reporting the ASP increases their knowledge of appropriate antimicrobial use in the ICU setting. Only 11% of respondents reported they felt that time spent interacting with the ASP team was an inefficient use of their time, and only 7% expressed concern that the ASP negatively affected their autonomy. CONCLUSION: Based on our survey results, Canadian intensivists are supportive of antimicrobial stewardship in ICUs and feel that ASPs provide a valuable service to both patients and clinicians.

Characteristics and Outcomes of Eligible Nonenrolled Patients in a Mechanical Ventilation Trial of Acute Respiratory Distress Syndrome.

RATIONALE: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion. OBJECTIVES: To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies. METHODS: Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group. CONCLUSIONS: Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.

Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

Coenrollment in a randomized trial of high-frequency oscillation: prevalence, patterns, predictors, and outcomes*.

OBJECTIVE: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial. DESIGN, SETTING, METHODS: We conducted an observational study nested within the OSCILLation for Acute Respiratory Distress Syndrome Treated Early Trial, which compared high-frequency oscillatory ventilation to conventional ventilation. We collected patient, center, and study data on coenrollment in randomized patients. Multilevel regression examined factors independently associated with coenrollment, considering clustering within centers. We examined the effect of coenrollment on safety and the trial outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 127 of 548 randomized patients (23.2%) were coenrolled in 25 unique studies. Coenrollment was reported in 17 of 39 centers (43.6%). Patients were most commonly coenrolled in one additional randomized clinical trial (76; 59.8%). Coenrollment was less likely in older patients (odds ratio, 0.87; 95% CI, 0.76-0.997), and in ICUs with greater than 26 beds (odds ratio, 0.56; 95% CI, 0.34-0.94), and more likely by investigators with more than 11 years of experience (odds ratio, 1.73; 95% CI, 1.06-2.82), by research coordinators with more than 8 years of experience (odds ratio, 1.87; 95% CI, 1.11-3.18) and in Canada (odds ratio, 4.66; 95% CI, 1.43-15.15). Serious adverse events were similar between coenrolled high-frequency oscillatory ventilation and control patients. Coenrollment did not modify the treatment effect of high-frequency oscillatory ventilation on hospital mortality. CONCLUSIONS: Coenrollment occurred in 23% of patients, commonly in younger patients, in smaller centers with more research infrastructure, and in Canada. Coenrollment did not influence patient safety or trial results.