Academic and Community ICUs Participating in a Critical Care Randomized Trial: A Comparison of Patient Characteristics and Trial Metrics.

Clinical research in Canada is conducted primarily in "academic" hospitals, whereas most clinical care is provided in "community" hospitals. The objective of this nested observational study was to compare patient characteristics, outcomes, process-of-care variables, and trial metrics for patients enrolled in a large randomized controlled trial who were admitted to academic and community hospitals in Canada. DESIGN: We conducted a preplanned observational study nested within the Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT, a randomized controlled trial comparing probiotics to placebo in mechanically ventilated patients) Research Program. SETTING: ICUs. PATIENTS: Mechanically ventilated patients. MEASUREMENTS: We compared patient characteristics, interventions, outcomes, and trial metrics between patients enrolled in PROSPECT from academic and community hospitals. MAIN RESULTS: Participating centers included 34 (82.9%) academic and seven (17.1%) community hospitals, which enrolled 2,203 (86.2%) and 352 (13.8%) patients, respectively. Compared with academic hospitals, patients enrolled in community hospitals were older (mean [sd] 62.7 yr [14.9 yr] vs 59.5 yr [16.4 yr]; p = 0.044), had longer ICU stays (median [interquartile range {IQR}], 13 d [8-23 d] vs 11 d [7-8 d]; p = 0.012) and higher mortality (percentage, [95% CI] in the ICU, 30.4% [25.8-35.4%]vs 20.5% [18.9-11.3%]; p = 0.002) and hospital (40.6% [35.6-45.8%] vs 26.1% [24.3-27.9%]; p < 0.001). Trial metrics, including informed consent rate (85.9% vs 76.3%; p = 0.149), mean (sd) monthly enrolment rate (2.1 [1.4] vs 1.1 [0.7]; p = 0.119), and protocol adherence (90.6% vs 91.6%; p = 0.207), were similar between community and academic ICUs. CONCLUSIONS: Community hospitals can conduct high-quality research, with similar trial metrics to academic hospitals. Patient characteristics differed between community and academic hospitals, highlighting the need for broader engagement of community hospitals in clinical research to ensure generalizability of study results.

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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.