scholarly journals Evaluating probiotics for the prevention of ventilator-associated pneumonia: a randomised placebo-controlled multicentre trial protocol and statistical analysis plan for PROSPECT

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e025228 ◽  
Author(s):  
Jennie Johnstone ◽  
Diane Heels-Ansdell ◽  
Lehana Thabane ◽  
Maureen Meade ◽  
John Marshall ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Controlled Trial ◽  
Statistical Analysis Plan ◽  
Hospital Length Of Stay ◽  
Sensitivity Analyses ◽  
Ventilator Associated Pneumonia ◽  
Increased Risk ◽  
The Impact

IntroductionVentilator-associated pneumonia (VAP) is the most common healthcare-associated infection in critically ill patients. Prior studies suggest that probiotics may reduce VAP and other infections in critically ill patients; however, most previous randomised trials were small, single centre studies. The Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) aims to determine the impact of the probioticLactobacillus rhamnosusGG on VAP and other clinically important outcomes in critically ill adults.MethodsPROSPECT is a multicentre, concealed, randomised, stratified, blinded, controlled trial in patients ≥18 years old, anticipated to be mechanically ventilated ≥72 hours, in intensive care units (ICUs) in Canada, the USA and Saudi Arabia. Patients receive either 1×1010 colony forming units ofL. rhamnosusGG twice daily or an identical appearing placebo. Those at increased risk of probiotic infection are excluded. The primary outcome is VAP. Secondary outcomes are other ICU-acquired infections includingClostridioides difficileinfection, diarrhoea (including antibiotic-associated diarrhoea), antimicrobial use, ICU and hospital length of stay and mortality. The planned sample size of 2650 patients is based on an estimated 15% VAP rate and will provide 80% power to detect a 25% relative risk reduction.Ethics and disseminationThis protocol and statistical analysis plan outlines the methodology, primary and secondary analyses, sensitivity analyses and subgroup analyses. PROSPECT is approved by Health Canada (#9427-M1133-45C), the research ethics boards of all participating hospitals and Public Health Ontario. Results will be disseminated via academic channels (peer reviewed journal publications, professional healthcare fora including international conferences) and conventional and social media. The results of PROSPECT will inform practice guidelines worldwide.Trialregistration numberNCT02462590; Pre-results.

scholarly journals Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis

2021 ◽  
Vol 23 (3) ◽  
pp. 273-284
Author(s):  
Laurent Billot ◽  
◽  
Jeffrey Lipman ◽  
Stephen J Brett ◽  
Jan J De Waele ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Randomised Controlled Trial ◽  
Data Collection ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Controlled Trial ◽  
Statistical Analysis Plan ◽  
Public Access ◽  
Phase 3 ◽  
Randomised Controlled

BACKGROUND: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis. OBJECTIVE: To describe a statistical analysis plan for the BLING III study. METHODS: The statistical analysis plan was designed by the trial statistician and chief investigators and approved by the BLING III management committee before the completion of data collection. Statistical analyses for primary, secondary and tertiary outcomes and planned subgroup analyses are described in detail. Interim analysis by the Data Safety and Monitoring Committee (DSMC) has been conducted in accordance with a pre-specified DSMC charter. RESULTS AND CONCLUSIONS: The statistical analysis plan for the BLING III study is published before completion of data collection and unblinding to minimise analysis bias and facilitate public access and transparent analysis and reporting of study findings. TRIAL REGISTRATION: ClinicalTrials.gov Registry NCT03212990.

scholarly journals Serum Procalcitonin Level and Mortality Risk in Critically ill Patients with Ventilator-Associated Pneumonia

2015 ◽  
Vol 37 (5) ◽  
pp. 1967-1972 ◽  
Author(s):  
Bo Li ◽  
Xin Zhao ◽  
Shumei Li
Keyword(s):  
Critically Ill ◽  
Mortality Risk ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
High Serum ◽  
Ventilator Associated Pneumonia ◽  
Prognostic Role ◽  
Procalcitonin Level ◽  
Increased Risk

Background/Aims: The prognostic role of serum procalcitonin level in critically ill patients with ventilator-associated pneumonia was unclear. The aim of our study was to investigate the relationship between serum procalcitonin level and mortality risk in critically ill patients with ventilator-associated pneumonia. Methods: Data of critically ill patients with ventilator-associated pneumonia were retrospectively collected. Demographics, comorbidities, and serum procalcitonin level were extracted from electronic medical records. The primary outcome was mortality within two months after diagnosis. Multivariable Cox regression analyses were performed to assess the prognostic role of serum procalcitonin level in those patients. Results: A total of 115 critically ill patients with ventilator-associated pneumonia were enrolled in our study. Serum procalcitonin level was not associated with age, gender, or other comorbidities. Univariate Cox regression model showed that high serum procalcitonin level was associated increased risk of morality within 2 months after diagnosis (OR = 2.32, 95% CI 1.25-4.31, P = 0.008). Multivariable Cox regression model showed that high serum procalcitonin level was independently associated increased risk of morality within 2 months after diagnosis (OR = 2.38, 95% CI 1.26-4.50, P = 0.008). Conclusion: High serum procalcitonin level is an independent prognostic biomarker of mortality risk in critically ill patients with ventilator-associated pneumonia, and it's a promising biomarker of prognosis in critically ill patients.

scholarly journals Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 918-925 ◽  
Author(s):  
Emma M Pinder ◽  
Anthony J Rostron ◽  
Thomas P Hellyer ◽  
Marie-Helene Ruchaud-Sparagano ◽  
Jonathan Scott ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Ex Vivo ◽  
Controlled Trial ◽  
Personalised Medicine ◽  
Common Adverse Event ◽  
Controlled Clinical Trial ◽  
Gm Csf ◽  
Hla Dr ◽  
Increased Risk

BackgroundCritically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired.MethodsThis was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 μg/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression and safety.ResultsThirty-eight patients were recruited from five intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis≥50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was fever.ConclusionsGM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.

The impact of oral care on oral health status and prevention of ventilator-associated pneumonia in critically ill patients

2017 ◽  
Vol 30 (2) ◽  
pp. 69-73 ◽  
Author(s):  
Abdullah Haghighi ◽  
Vida Shafipour ◽  
Masoumeh Bagheri-Nesami ◽  
Afshin Gholipour Baradari ◽  
Jamshid Yazdani Charati
Keyword(s):  
Health Status ◽  
Oral Health ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Oral Care ◽  
Oral Health Status ◽  
Ventilator Associated Pneumonia ◽  
The Impact

scholarly journals American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate intensity anticoagulation in critically ill patients

2021 ◽  
Author(s):  
Adam Cuker ◽  
Eric K. Tseng ◽  
Robby Nieuwlaat ◽  
Pantep Angchaisuksiri ◽  
Clifton Blair ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Health Care Professionals ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
American Society ◽  
The Impact

Background: COVID-19 related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel, including three patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 5, 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. Results: The panel agreed on one additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19 related-critical illness who do not have confirmed or suspected VTE. Conclusions: This recommendation was based on low certainty in the evidence, underscoring the need for further high-quality, randomized controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence on predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of non-anticoagulant therapies (e.g., antiviral agents, corticosteroids) on thrombotic risk.

Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial

2020 ◽  
Vol 22 (2) ◽  
pp. 133-141
Author(s):  
Alexis P Poole ◽  
◽  
Mark E Finnis ◽  
James Anstey ◽  
Rinaldo Bellomo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Intensive Care ◽  
Blood Glucose ◽  
Statistical Analysis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Analysis Plan

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial — the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial — which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0–14.0 mmol/L) or usual care (target 6.0–10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

scholarly journals Delirium and Associated Length of Stay and Costs in Critically Ill Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Claudia Dziegielewski ◽  
Charlenn Skead ◽  
Toros Canturk ◽  
Colleen Webber ◽  
Shannon M. Fernando ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Hospital Costs ◽  
Hospital Length ◽  
Mean Difference ◽  
Hospital Length Of Stay ◽  
The Mean ◽  
The Impact

Purpose. Delirium frequently affects critically ill patients in the intensive care unit (ICU). The purpose of this study is to evaluate the impact of delirium on ICU and hospital length of stay (LOS) and perform a cost analysis. Materials and Methods. Prospective studies and randomized controlled trials of patients in the ICU with delirium published between January 1, 2015, and December 31, 2020, were evaluated. Outcome variables including ICU and hospital LOS were obtained, and ICU and hospital costs were derived from the respective LOS. Results. Forty-one studies met inclusion criteria. The mean difference of ICU LOS between patients with and without delirium was significant at 4.77 days ( p < 0.001 ); for hospital LOS, this was significant at 6.67 days ( p < 0.001 ). Cost data were extractable for 27 studies in which both ICU and hospital LOS were available. The mean difference of ICU costs between patients with and without delirium was significant at $3,921 ( p < 0.001 ); for hospital costs, the mean difference was $5,936 ( p < 0.001 ). Conclusion. ICU and hospital LOS and associated costs were significantly higher for patients with delirium, compared to those without delirium. Further research is necessary to elucidate other determinants of increased costs and cost-reducing strategies for critically ill patients with delirium. This can provide insight into the required resources for the prevention of delirium, which may contribute to decreasing healthcare expenditure while optimizing the quality of care.

scholarly journals Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective observational study

2020 ◽  
Author(s):  
Hiromu Naraba ◽  
Tadahiro Goto ◽  
Toru Shirakawa ◽  
Tomohiro Sonoo ◽  
Naoki Kanda ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Observational Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Tertiary Care ◽  
Cox Proportional Hazards Model ◽  
Retrospective Observational Study ◽  
Sensitivity Analyses ◽  
Increased Risk ◽  
Blood Glucose Range

Objective: Time in targeted blood glucose range (TIR) 70-140 mg/dL has been associated with an increased risk of mortality in critically ill patients. Nevertheless, it remains unclear whether TIR is associated with 28-day mortality in critically ill patients under glycemic control with a less tight target glucose range of 70-180 mg/dL. We aimed to assess whether TIR 70-180 mg/dL was associated with 28-day mortality and to identify the optimal TIR. Design: A retrospective observational study. Setting: Data from a tertiary care centre in Japan, from 1 January 2016 through 31 October 2019. Participants: 1,230 adult patients admitted to the intensive care unit for more than three days. Outcome measure: The primary outcome was 28-day mortality. Results: Of 1,230 patients, patients with HbA1c ≥6.5% had a higher 28-day mortality than those with <6.5% (32.0% vs. 22.7%; p=0.003). In the multivariate logistic regression, TIR <80% was associated with an increased risk of 28-day mortality in patients with HbA1c <6.5% with an adjusted odds ratio (OR) of 1.88 (95% confidence interval [CI]: 1.36-2.61). When using 10% incremental TIR as a categorical variable, lower TIR was associated with worse 28-day mortality compared to TIR ≥90% in patients with HbA1c <6.5% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36-5.53]). Similar associations were found in the analyses using the COX proportional hazards model. In addition, sensitivity analyses using TIR of the first three days showed that the overall associations were consistent with primary analyses. Conclusions: Our study demonstrated that lower TIR 70-180 mg/dL was associated with higher 28-day mortality in nondiabetic critically ill patients.

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