Evaluating the impact of a SIMPlified LaYered consent process on recruitment of potential participants to the Staphylococcus aureus Network Adaptive Platform trial: study protocol for a multicentre pragmatic nested randomised clinical trial (SIMPLY-SNAP trial).

INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).

Non-inferiority trial of a shorter (7 days) compared with a longer (14 days) duration of antimicrobial therapy for the treatment of bacteraemic urinary sepsis, measured by microbiological success after the completion of therapy: a substudy protocol for the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) multicentre randomised controlled trial.

INTRODUCTION: The BALANCE study is a randomised clinical trial (3626 participants) designed to assess the non-inferiority of 7 days (short-course) antibiotic therapy compared with 14 days of therapy for bacteraemia using the pragmatic endpoint of 90-day survival. Based on pilot study data, approximately 30% of enrolees will have a urinary tract infection (UTI) as the source of bacteraemia. METHODS AND ANALYSIS: We aim to assess the non-inferiority of short-course antibiotic therapy for patients with bacteraemia UTIs.Participating sites in four countries will be invited to join this substudy. All participants of this substudy will be enrolled in the main BALANCE study. The intervention will be assigned and treatment administered as specified in the main protocol.We will include participants in this substudy if the probable source of their infection is a UTI, as judged by the site principal investigator, and they have a urine microscopy and culture indicative of a UTI. Participants will be excluded if they have an ileal loop, vesicoureteric reflux or suspected or confirmed prostatitis.The primary outcome is the absence of a positive culture on a test-of-cure urine sample collected 6-12 days after cessation of antimicrobials, with a non-inferiority margin of 15%. Secondary outcomes include the clinical resolution of infection symptoms at test-of-cure. ETHICS AND DISSEMINATION: The study has been approved in conjunction with the main BALANCE study through the relevant ethics review process at each participating site. We will disseminate the results through the Australasian Society for Infectious Diseases, Canadian Critical Care Trials Group, the Association for Medical Microbiology and Infectious Diseases Canada Clinical Research Network (AMMI Canada CRN) and other collaborators. UNIVERSAL TRIAL NUMBER: U1111-1256-0874. MAIN BALANCE TRIAL REGISTRATION: NCT03005145. TRIAL REGISTRATION NUMBER: Australian Clinical Trial Register: ACTRN12620001108909.

Closed loop communication in the trauma bay: identifying opportunities for team performance improvement through a video review analysis.

OBJECTIVES: Communication among trauma team members in the trauma bay is vulnerable to errors, which may impact patient outcomes. We used the previously validated trauma-non-technical skills (T-NOTECHS) tool to identify communication gaps during patient management in the trauma bay and to inform development strategies to improve team performance. METHODS: Two reviewers independently assessed non-technical skills of team members through video footage at Sunnybrook Health Sciences Centre. Team performance was measured using T-NOTECHS across five domains using a five-point Likert scale (lower score indicating worse performance): (1) leadership; (2) cooperation and resource management; (3) communication and interaction; (4) assessment and decision making; (5) situation awareness/coping with stress. Secondary outcomes assessed the number of callouts, closed loop communications and parallel conversations. RESULTS: The study included 55 trauma activations. Injury severity score (ISS) was used as a measure of trauma severity. A case with an ISS score ≥ 16 was considered severe. ISS was ≥ 16 in 37% of cases. Communication and interaction scored significantly lower compared to all other domains (p < 0.0001). There were significantly more callouts and completed closed loop communications in more severe cases compared to less severe cases (p = 0.017 for both). Incomplete closed loop communications and parallel conversations were identified, irrespective of case severity. CONCLUSION: A lower communication score was identified using T-NOTECHS, attributed to incomplete closed loop communications and parallel conversations. Through video review of trauma team activations, opportunities for improvement in communication can be identified by the T-NOTECHS tool, as well as specifically identifying callouts and closed loop communication. This process may be useful for trauma programs as part of a quality improvement program on communication skills and team performance.

RéSUMé: OBJECTIFS : La communication entre les membres de l'équipe de traumatologie dans la salle de traumatologie est vulnérable aux erreurs, ce qui peut avoir un impact sur les résultats des patients. Nous avons utilisé l'outil de compétences non techniques en traumatologie (T-NOTECHS) précédemment validé pour identifier les lacunes en matière de communication pendant la prise en charge des patients dans la salle de traumatologie et pour informer les stratégies de développement visant à améliorer les performances de l'équipe. MéTHODES: Deux examinateurs ont évalué de manière indépendante les compétences non techniques des membres de l'équipe au moyen de séquences vidéo réalisées au Sunnybrook Health Sciences Centre. La performance de l'équipe a été mesurée à l'aide de la T-NOTECHS dans cinq domaines à l'aide d'une échelle de Likert à cinq points (un score plus bas indiquant une performance plus faible) : (1) leadership ; (2) coopération et gestion des ressources ; (3) communication et interaction ; (4) évaluation et prise de décision ; (5) conscience de la situation/ gestion du stress. Les résultats secondaires ont évalué le nombre d'appels, de communications en boucle fermée et de conversations parallèles. RéSULTATS: L'étude a porté sur 55 activations de traumatismes. Le score de gravité des blessures (ISS) a été utilisé comme mesure de la gravité du traumatisme. Un cas présentant un score ISS ≥ 16 était considéré comme grave. L'ISS était ≥ 16 dans 37 % des cas. La communication et l'interaction ont obtenu des scores significativement plus faibles par rapport à tous les autres domaines (p<0,0001). Il y avait significativement plus d'appels et de communications en boucle fermée terminées dans les cas plus graves que dans les cas moins graves (p = 0.017 pour les deux). Des communications incomplètes en boucle fermée et des conversations parallèles ont été identifiées, indépendamment de la gravité du cas. CONCLUSION: Un score de communication plus faible a été identifié en utilisant le T-NOTECHS, attribué à des communications incomplètes en boucle fermée et à des conversations parallèles. Grâce à l'examen vidéo des activations de l'équipe de traumatologie, les possibilités d'amélioration de la communication peuvent être identifiées par l'outil T-NOTECHS, ainsi que l'identification spécifique des appels et de la communication en boucle fermée. Ce processus peut être utile pour les programmes de traumatologie dans le cadre d'un programme d'amélioration de la qualité sur les compétences de communication et la performance de l'équipe.

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

INTRODUCTION: Bloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied. METHODS AND ANALYSIS: We will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (Staphylococcus aureus, Staphylococcus lugdunensis, Candida and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study results via the Canadian Critical Care Trials Group and other collaborating networks to set the global paradigm for antibiotic treatment duration for non-staphylococcal Gram-positive, Gram-negative and anaerobic bacteraemia, among patients admitted to hospital. TRIAL REGISTRATION NUMBER: The BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial was registered at www.clinicaltrials.gov (registration number: NCT03005145).

A study protocol for an observational cohort investigating COGnitive outcomes and WELLness in survivors of critical illness: the COGWELL study.

INTRODUCTION: Up to 9 out of 10 intensive care unit (ICU) survivors will suffer some degree of cognitive impairment at hospital discharge and approximately half will have decrements that persist for years. The mechanisms for this newly acquired brain injury are poorly understood. The purpose of this study is to describe the prevalence of sleep abnormalities and their association with cognitive impairment, examine a well-known genetic risk factor for dementia (Apolipoprotein E ε4) that may allow for genetic risk stratification of ICU survivors at greatest risk of cognitive impairment and determine if electroencephalography (EEG) is an independent predictor of long-term cognitive impairment and possibly a candidate intermediate end point for future clinical trials. METHODS AND ANALYSIS: This is a multisite, prospective, observational cohort study. The setting for this trial will be medical and surgical ICUs of five large tertiary care referral centres. The participants will be adult patients admitted to a study ICU and invasively ventilated for ≥3 days . Participants will undergo follow-up within 7 days of ICU discharge, 6 months and 1 year. At each time point, patients will have an EEG, blood work (biomarkers; gene studies), sleep study (actigraphy), complete a number of questionnaires as well as undergo neuropsychological testing. The primary outcome of this study will be long-term cognitive function at 12 months follow-up as measured by the Repeatable Battery for the Assessment of Neuropsychological Status and Trails Making Test B. ETHICS AND DISSEMINATION: The study has received the following approvals: University Health Network Research Ethics Committee (13-6425-BE), Sunnybrook Health Centre Research Ethics Committee (365-2013), Mount Sinai Research Ethics Committee (14-0194-E) and St. Michael's Hospital Research Ethics Committee (14-295). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers. TRIAL REGISTRATION NUMBER: NCT02086877; Pre-results.

Long-Term Outcomes and Health Care Utilization after Prolonged Mechanical Ventilation.

RATIONALE: Limited data are available to characterize the long-term outcomes and associated costs for patients who require prolonged mechanical ventilation (PMV; defined here as mechanical ventilation for longer than 21 d). OBJECTIVES: To examine the association between PMV and mortality, health care utilization, and costs after critical illness. METHODS: Population-based cohort study of adults who received mechanical ventilation in an intensive care unit (ICU) in Ontario, Canada between 2002 and 2013. MEASUREMENT AND MAIN RESULTS: We used linked administrative databases to determine discharge disposition, and ascertain 1-year mortality (primary outcome), readmissions to hospital and ICU, and health care costs for hospital survivors. Overall, 11,594 (5.4%) patients underwent PMV, with 42.4% of patients dying in the hospital (vs. 27.6% of patients who did not undergo prolonged ventilation; P < 0.0001). Patients on prolonged ventilation were more frequently discharged to other facilities or home with health care support (84.8 vs. 43.5%, P < 0.0001). Among hospital survivors, estimated mortality was higher for patients who underwent PMV: 16.6 versus 11% at 1 year and 42.0 versus 30.4% at 5 years. At 1 year after hospital discharge, patients on prolonged ventilation had higher rates of hospital readmission (47.2 vs. 37.7%; adjusted odds ratio = 1.20; 95% confidence interval = 1.14-1.26), ICU readmission (19.0 vs. 11.6%; adjusted odds ratio = 1.49; 95% confidence interval: 1.39, 1.60), and total health care costs: median (interquartile range) Can $32,526 ($20,821-$56,102) versus Can $13,657 ($5,946-$38,022). Increasing duration of mechanical ventilation was associated with higher mortality and health care utilization. CONCLUSIONS: Critically ill patients who undergo mechanical ventilation in an ICU for longer than 21 days have high in-hospital mortality and greater postdischarge mortality, health care utilization, and health care costs compared with patients who undergo mechanical ventilation for a shorter period of time.

Airway Management Strategies for Brain-injured Patients Meeting Standard Criteria to Consider Extubation. A Prospective Cohort Study.

RATIONALE: Patients with acute brain injury are frequently capable of breathing spontaneously with minimal ventilatory support despite persistent neurological impairment. OBJECTIVES: We sought to describe factors associated with extubation timing, success, and primary tracheostomy in these patients. METHODS: We conducted a prospective multicenter observational cohort study in three academic hospitals in Toronto, Canada. Consecutive brain-injured adults receiving mechanical ventilation for at least 24 hours in three intensive care units were screened by study personnel daily for extubation consideration criteria. We monitored all patients until hospital discharge and used logistic regression models to examine associations with extubation failure and delayed extubation. MEASUREMENTS AND MAIN RESULTS: Of 192 patients included, 152 (79%) were extubated and 40 (21%) received a tracheostomy without an extubation attempt. The rate of extubation failure within 72 hours was 32 of 152 (21%), which did not vary significantly between those extubated before (early; 6 of 37; 16.2%), within 24 hours (timely; 14 of 70; 20.0%), or more than 24 hours after meeting criteria to consider extubation (delayed; 12 of 45; 26.7%; P = 0.49). Delayed extubation was associated with lower a Glasgow Coma Scale (GCS) score at the time of consideration of extubation, absence of cough, and new positive sputum cultures. Factors independently associated with successful extubation were presence of cough (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.42-9.09), fluid balance in prior 24 hours (OR, 0.75 per 1-L increase; 95% CI, 0.57-0.98), and age (OR, 0.97 per 10-yr increase; 95% CI, 0.95-0.99). A higher GCS score was not associated with successful extubation. CONCLUSIONS: Extubation success was predicted by younger age, presence of cough, and negative fluid balance, rather than GCS score at extubation. These results do not support prolonging intubation solely for low GCS score in brain-injured patients.