Frequency of screening and SBT Technique Trial-North American Weaning Collaboration (FAST-NAWC): an update to the protocol and statistical analysis plan.

BACKGROUND: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units. METHODS/DESIGN: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis. TRIAL REGISTRATION: Clinical Trials.gov NCT02399267.

Predictors of response following standardized education and self-management recommendations for low back pain stratified by dominant pain location.

BACKGROUND: Low back pain (LBP) is a leading cause of disability globally. Risk-stratification systems (e.g. STarT Back) have been proposed to guide treatment, but with varying success. We investigated factors associated with poor response to standardized LBP education and self-management recommendations stratified by dominant pain location (back or leg). METHODS: LBP patients underwent a standardized primary care model of care of education and self-management recommendations. Poor response was defined as an Oswestry Disability Index (ODI) change score <10 units by 6 months. Multivariable logistic regression was used to identify poor response risk factors, stratified by back-dominant and leg-dominant back pain. Baseline factors: age, sex, body mass index, ODI, LBP/leg-pain intensity, LBP/leg-pain duration, STarT Back chronicity-risk, smoking, comorbidity count, and self-efficacy. RESULTS: The sample consisted of 767 patients (443 back-dominant, 324 leg-dominant). Mean age was 53 years, and 59% were female. Females accounted for 66% of back-dominant and 50% of leg-dominant patients. Chronicity risk was 'high' for 18% of back-dominant and 29% of leg-dominant patients. Poor response was higher in back- (57%) compared to leg-dominant (42%) patients. Adjusted stratified analyses: female sex, moderate or high chronicity-risk, and increasing age were associated with increased risk of poor response, and greater self-efficacy with favourable response, in leg-dominant patients; these were not the cases among back-dominant patients. Increased comorbidity count was associated with poor response in back dominant patients. In both patient groups, higher baseline ODI score was associated with favorable response, and smoking and longer pain duration with poor response. CONCLUSIONS: Differences in the influence of sex and chronicity risk in particular on outcome by dominant pain location suggests that considering these patients as a single group may not be appropriate. Furthermore, findings suggest that stratification by pain dominance may enhance the use of established risk stratification tools such as the STarT Back.

Frequency of Screening for Weaning From Mechanical Ventilation: Two Contemporaneous Proof-of-Principle Randomized Controlled Trials.

OBJECTIVES: It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context. DESIGN: We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients. SETTING: Ten and 11 ICUs in Canada, respectively. PATIENTS: Parallel trials of younger (RELEASE < 65 yr) and older (SENIOR ≥ 65 yr) critically ill adults invasively ventilated for at least 24 hours. INTERVENTIONS: Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists. MEASUREMENTS AND MAIN RESULTS: In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined. CONCLUSIONS: Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Trials directly comparing alternative spontaneous breathing trial techniques: a systematic review and meta-analysis.

BACKGROUND: The effect of alternative spontaneous breathing trial (SBT) techniques on extubation success and other clinically important outcomes is uncertain. METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, Evidence-Based Medicine Reviews, Ovid Health Star, proceedings of five conferences (1990-2016), and reference lists for randomized trials comparing SBT techniques in intubated adults or children. Primary outcomes were initial SBT success, extubation success, or reintubation. Two reviewers independently screened citations, assessed trial quality, and abstracted data. RESULTS: We identified 31 trials (n = 3541 patients). Moderate-quality evidence showed that patients undergoing pressure support (PS) compared with T-piece SBTs (nine trials, n = 1901) were as likely to pass an initial SBT (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.89-1.11; I 2 = 77%) but more likely to be ultimately extubated successfully (RR 1.06, 95% CI 1.02-1.10; 11 trials, n = 1904; I 2 = 0%). Exclusion of one trial with inconsistent results for SBT and extubation outcomes suggested that PS (vs T-piece) SBTs also improved initial SBT success (RR 1.06, 95% CI 1.01-1.12; I 2 = 0%). Limited data suggest that automatic tube compensation plus continuous positive airway pressure (CPAP) vs CPAP alone or PS increase SBT but not extubation success. CONCLUSIONS: Patients undergoing PS (vs T-piece) SBTs appear to be 6% (95% CI 2-10%) more likely to be extubated successfully and, if the results of an outlier trial are excluded, 6% (95% CI 1-12%) more likely to pass an SBT. Future trials should investigate patients for whom SBT and extubation outcomes are uncertain and compare techniques that maximize differences in support.