Methods proposed for monitoring the implementation of evidence-based research: a cross-sectional study.

OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

Multistudy Research Operations in the ICU: An Interprofessional Pandemic-Informed Approach.

Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN: Two-phase, single-center multistudy cohort. SETTING: University-affiliated ICU in Hamilton, ON, Canada. PATIENTS: Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS: Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.

Diarrhea during critical illness: a multicenter cohort study.

PURPOSE: To study the incidence, predictors, and outcomes of diarrhea during the stay in the intensive care unit (ICU). METHODS: Prospective cohort of consecutive adults in the ICU for > 24 h during a 10-week period across 12 intensive care units (ICUs) internationally. The explored outcomes were: (1) incidence of diarrhea, (2) Clostridioides difficile-associated diarrhea (CDAD); (3) ICU and hospital length of stay (LOS) and mortality in patients with diarrhea. We fit generalized linear models to evaluate the predictors, management, morbidity and mortality associated with diarrhea. RESULTS: Among 1109 patients aged 61.4 (17.5) [mean (standard deviation)] years, 981(88.5%) were medical and 645 (58.2%) were mechanically ventilated. The incidence was 73.8% (818 patients, 73.8%, 95% confidence interval [CI] 71.1-76.6) using the definition of the World Health Organisation (WHO). Incidence varied across definitions (Bristol 53.5%, 95% CI 50.4-56.7; Bliss 37.7%, 95% CI 34.9-40.4). Of 99 patients with diarrhea undergoing CDAD testing, 23 tested positive (2.2% incidence, 95% CI 1.5-3.4). Independent predictors included enteral nutrition (RR 1.23, 95% CI 1.16-1.31, p < 0.001), antibiotic days (RR 1.02, 95% CI 1.02-1.03, p < 0.001), and suppositories (RR 1.14 95% CI 1.06-1.22, p < 0.001). Opiates decreased diarrhea risk (RR 0.76, 95% CI 0.68-0.86, p < 0.001). Diarrhea prompted management modifications (altered enteral nutrition or medications: RR 10.25, 95% CI 5.14-20.45, p < 0.001) or other consequences (fecal management device or CDAD testing: RR 6.16, 95% CI 3.4-11.17, p < 0.001). Diarrhea was associated with a longer time to discharge for ICU or hospital stay, but was not associated with hospital mortality. CONCLUSION: Diarrhea is common, has several predictors, and prompts changes in patient care, is associated with longer time to discharge but not mortality.

Cuff Leak Test and Airway Obstruction in Mechanically Ventilated Intensive Care Unit Patients: A Pilot Randomized Controlled Clinical Trial.

Rationale: Laryngeal edema is a known complication of endotracheal intubation that may cause airway obstruction upon extubation. The only test available to predict this complication is the cuff leak test (CLT). Objectives: Given the uncertainty of the CLT's clinical utility, we conducted the COMIC (Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients) pilot study to examine the feasibility of undertaking a larger trial. Methods: COMIC is a multicentered, parallel-group randomized trial performed in Canada, Saudi Arabia, and Poland. We enrolled mechanically ventilated adults admitted to the intensive care unit who were deemed ready for extubation. Those allocated to the intervention arm had the results of their CLT communicated to the healthcare team, who then decided to proceed with extubation or not. In those randomized to the control arm, the CLT results were not communicated to the healthcare team and patients were extubated, regardless of the CLT result. The primary outcomes focused on feasibility. Results: One hundred patients (56 in the intervention and 44 in the control arm) were enrolled. All feasibility criteria were met, including 1) recruitment rate of 7.6 patients/month, 2) consent rate of 88.3% (95% confidence interval [CI], 82.1-94.5%), and 3) protocol adherence of 98% (95% CI, 95-100%). There were two episodes of clinically significant stridor in the intervention group and four patients who required reintubation in each group. Conclusions: The results of the COMIC pilot trial support the feasibility of a larger trial to determine the effect of the CLT on reintubation and clinically important stridor.Clinical trial registered with www.clinicaltrials.gov (NCT03372707).

Scale-up and sustainability of a personalized end-of-life care intervention: a longitudinal mixed-methods study.

BACKGROUND: Scaling-up and sustaining healthcare interventions can be challenging. Our objective was to describe how the 3 Wishes Project (3WP), a personalized end-of-life intervention, was scaled-up and sustained in an intensive care unit (ICU). METHODS: In a longitudinal mixed-methods study from January 12,013 - December 31, 2018, dying patients and families were invited to participate if the probability of patient death was > 95% or after a decision to withdraw life support. A research team member or bedside clinician learned more about each of the patients and their family, then elicited and implemented at least 3 personalized wishes for patients and/or family members. We used a qualitative descriptive approach to analyze interviews and focus groups conducted with 25 clinicians who cared for the enrolled patients. We used descriptive statistics to summarize patient, wish, and clinician characteristics, and analyzed outcome data in quarters using Statistical Process Control charts. The primary outcome was enrollment of terminally ill patients and respective families; the secondary outcome was the number of wishes per patient; tertiary outcomes included wish features and stakeholder involvement. RESULTS: Both qualitative and quantitative analyses suggested a three-phase approach to the scale-up of this intervention during which 369 dying patients were enrolled, having 2039 terminal wishes implemented. From a research project to clinical program to an approach to practice, we documented a three-fold increase in enrolment with a five-fold increase in total wishes implemented, without a change in cost. Beginning as a study, the protocol provided structure; starting gradually enabled frontline staff to experience and recognize the value of acts of compassion for patients, families, and clinicians. The transition to a clinical program was marked by handover from the research staff to bedside staff, whereby project catalysts mentored project champions to create staff partnerships, and family engagement became more intentional. The final transition involved empowering staff to integrate the program as an approach to care, expanding it within and beyond the organization. CONCLUSIONS: The 3WP is an end-of-life intervention which was implemented as a study, scaled-up into a clinical program, and sustained by becoming integrated into practice as an approach to care.

Quality and methodology of clinical practice guidelines on antiviral pharmacotherapy for COVID­19 during the early phase of the pandemic.

INTRODUCTION: Despite availability of reliable guidelines development methods, the risk of producing less reliable documents may be higher when the guidelines are developed rapidly. OBJECTIVES: The aim of this study was to assess quality of guidelines on coronavirus disease 2019 (COVID-19), developed in the early stages of COVID-19 pandemic and assess if recommendations for pharmacotherapy were supported by evidence. METHODS: We performed the search for documents, that considered antiviral therapies and contained a recommendations for clinicians. The quality of the guidelines was assessed using the AGREE II-Global Rating Scale Instrument and series of additional criteria. RESULTS: The analysis included 40 publications. The median of quality of documents assessed with the AGREE II-GRS tool was 2.0 (interquartile range 1.5-2.5). Most documents did not fulfill the rigour of guideline development quality criteria. The AGREE II-GRS scores did not differ significantly across the type of the document, issuing institution and the mode of publication. 75% of documents provided recommendations for the use of antiviral medications despite apparent lack of sufficient evidence supporting such treatments. Of the included documents, 75% were not updated within the 2 months after the publication of the first randomized controlled trial on COVID-19 antiviral therapy. CONCLUSIONS: Most guidelines or guidance documents published during the early phase of the COVID-19 pandemic were of poor quality, contained recommendations for the use of antiviral therapy for SARS-CoV-2 infection despite only very low quality of evidence available, and were not updated on a regular basis.

The cuff leak test in critically ill patients: An international survey of intensivists.

BACKGROUND: The cuff leak test (CLT) is used to assess laryngeal edema prior to extubation. There is limited evidence for its diagnostic accuracy and conflicting guidelines surrounding its use in critically ill patients who do not have risk factors for laryngeal edema. The primary study aim was to describe intensivists' beliefs, attitudes, and practice regarding the use of the CLT. METHODS: A 13-item survey was developed, pilot-tested, and subjected to clinical sensibility testing. The survey was distributed electronically through MetaClinician®. Descriptive statistics and multivariable regression analysis were performed to examine associations between participant demographics and survey responses. RESULTS: 1184 practicing intensivists from 17 countries in North and South America, Europe, Oceania, and Asia participated. The majority (59%) of respondents reported rarely or never perform the CLT prior to extubating patients not at high risk of laryngeal edema, which correlated with 54% of respondents reporting they believed a failed CLT did not predict reintubation. Intensivists from the Middle East were 2.4 times more likely to request a CLT compared to those from North America. Intensivists with base training in medicine or emergency medicine were more likely to request a CLT prior to extubation compared to those with base training in anesthesiology. CONCLUSION: Use of the CLT prior to extubating patients not at high risk of laryngeal edema in the intensive care unit is highly variable. Practice appears to be influenced by country of practice and base specialty training.

GRADE guidelines: 21 part 1. Study design, risk of bias, and indirectness in rating the certainty across a body of evidence for test accuracy.

OBJECTIVES: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can assess the results and the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA). STUDY DESIGN AND SETTING: We present an overview of the GRADE approach and guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Part 1 of the two parts in this 21st guidance article about how to apply GRADE focuses on understanding study design issues in test accuracy, provide an overview of the domains, and describe risk of bias and indirectness specifically. RESULTS: Supplemented by practical examples, we describe how raters of the evidence using GRADE can evaluate study designs focusing on tests and how they apply the GRADE domains risk of bias and indirectness to a body of evidence of TA studies. CONCLUSION: Rating the certainty of a body of evidence using GRADE in Cochrane and other reviews and World Health Organization and other guidelines dealing with in TA studies helped refining our approach. The resulting guidance will help applying GRADE successfully for questions and recommendations focusing on tests.

GRADE guidelines: 21 part 2. Test accuracy: inconsistency, imprecision, publication bias, and other domains for rating the certainty of evidence and presenting it in evidence profiles and summary of findings tables.

OBJECTIVES: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can rate the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias, and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables. STUDY DESIGN AND SETTING: We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. RESULTS: Supplemented by practical examples, we describe how raters of the evidence can apply the GRADE domains inconsistency, imprecision, and publication bias to a body of evidence of TA studies. CONCLUSION: Using GRADE in Cochrane and other reviews as well as World Health Organization and other guidelines helped refining the GRADE approach for rating the certainty of a body of evidence from TA studies. Although several of the GRADE domains (e.g., imprecision and magnitude of the association) require further methodological research to help operationalize them, judgments need to be made on the basis of what is known so far.