PROSPECT Update & Recent Publications Deborah Cook

1. PROSPECT Update & Recent Publications Deborah Cook

2. A critical care intervention available over the counter!

3. Investigator-Initiated Trials: 10 Attributes 1. Address some common problems in practice 2. Evaluate widely available drugs & devices 3. Embrace broader patient & family concerns 4. Not motivated by increasing market share 5. Preserve researcher independence 6. Rationalize research bureaucracy 7. Less well funded than industry, but cost less too 8. Reflect carefully on coenrolment 9. Enable individual patient data meta-analyses 10. Foster academic education & enrichment

5. Probiotics in ICU Research Program Probiotic Capsule Quality Control PROSPECT Pilot RCT N=150 & Vanguard N=150 Total = 300 PhD Protocol Pilot RCT PROSPECT-TIMES (Time In Motion Evaluation Study) PROSPECT Main RCT Probiotics Hamilton Audit Inter-Prob (Interviewing the Public on Probiotics) Pro-Surve (Probiotic Survey Of Pharmacists) DICE (diarrhea - JD) Probiotics Systematic Review Mechanistic Sub-study N=42 ACCIDIC (C difficile - ED) EconomicEvaluation Serum Markers of Inflammation & Microbiome Feasibility Substudy Practice Guideline

8. Physicians Services Inc. Grant • To help transition the pilot trial into the vanguard phase of the main trial • To facilitate career development in clinical trials for Dr Jennie Johnstone • To support ICUs enrolling in PROSPECT in Ontario, including community centers

9. CIHR Meeting Grant 1) To review the PROSPECT Pilot results 2) To review the Main trial protocol 3) To generate any new substudies & grants 4) To create experiential educational opportunities for new investigators and HQPs (‘on the ground’ research conduct)

10. TVN Canadian Frailty Network 1) To evaluate the effect of probiotics in critically ill patients >65 years of age (~40% total sample) …..and as per Transformative Grant mandate 2) To learn about pre-ICU frailty amongst adult critically ill patients (main trial, ~80% sample) 3) To train 4 highly qualified personnel • Erick Duan, Joanna Dionne, Daphnee Lamarche, Melissa Shears

11. Frailty • Incorporating 9-point Clinical Frailty Scale • A multidimensional syndrome characterized by a decline in physiologic and cognitive reserve that increases susceptibility to adverse events and unfavourable outcomes, often following relatively minor stressors • “Frailty needs to be recognized and integrated into management of selected younger patients admitted to the ICU, and not just the elderly.”[Bagshaw, Crit Care 2016]

12. Am J Resp Crit Care Med 2015

13. Strategy with best cost-benefit ratio:+Suction ETT + IHI Bundle with oral care + Probiotics2014 Compendium of Strategies to Prevent Healthcare Associated Infections in Acute Care Hospitals Am J Resp Crit Care Med 2015

14. Design: Randomized open label RCT in 235 adults • Patients: Expected to receive MV >48h • Bacillus subtilis+Enterococcus faecalis 0.5g tid x 14days Less VAP: 36.4 vs 50.4%, p=0.031 Later Time to VAP 10.4 vs 7.5 days, p=0.022 Fewer gastric PPMO 24.0 vs 44.0%, p=0.004 Intensive Care Medicine 2016

15. Design: Randomized open label trial of 100 adults, including 70 with 3 serial specimens • Patients: cardiac + medical ICU (~60% MV) • Lactobacillus rhamnosus GG bid • No difference in the loss or acquisition of MRDO Infect Control & Hospital Epidemiology 2015