Publications by authors named "Finfer S"
Purpose: To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings.
Methods: An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an international panel of clinicians and researchers with expertise in sepsis management.
Background: The combination of intravenous hydrocortisone and enteral fludrocortisone may reduce mortality in patients with septic shock. The optimal dose and reliability of absorption of fludrocortisone in critically ill patients are unclear.
Methods: In a multi-centre, open label, phase II randomized clinical trial, intravenous hydrocortisone alone or in combination with one of three doses of enteral fludrocortisone (50 µg, 100 µg or 200 µg daily) for 7 days was compared in patients with septic shock.
Background: The diagnostic performance of the available risk assessment models for VTE in patients who are critically ill receiving pharmacologic thromboprophylaxis is unclear.
Research Question: For patients who are critically ill receiving pharmacologic thromboprophylaxis, do risk assessment models predict who would develop VTE or who could benefit from adjunctive pneumatic compression for thromboprophylaxis?
Study Design And Methods: In this post hoc analysis of the Pneumatic Compression for Preventing VTE (PREVENT) trial, different risk assessment models for VTE (ICU-VTE, Kucher, Intermountain, Caprini, Padua, and International Medical Prevention Registry on VTE [IMPROVE] models) were evaluated. Receiver-operating characteristic curves were constructed, and the sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated.
Article Synopsis
- A study was conducted to evaluate the effects of the proton-pump inhibitor pantoprazole on critically ill patients undergoing invasive ventilation, comparing it to a placebo.
- The trial included 4,821 patients and found that pantoprazole significantly reduced the incidence of clinically important upper gastrointestinal bleeding compared to placebo (1.0% vs. 3.5%).
- However, there was no significant difference in overall mortality rates at 90 days between the pantoprazole group (29.1%) and the placebo group (30.9%).
Background: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients.
Methods: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses.
Background: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available.
Methods: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults.
Article Synopsis
- A study investigated if continuous infusion of β-lactam antibiotics reduces death risk in critically ill sepsis patients, comparing this method to intermittent infusion.
- Conducted in 104 ICUs across several countries from 2018 to 2023, the trial involved over 7,200 participants receiving either piperacillin-tazobactam or meropenem.
- Results showed a slight decrease in 90-day mortality for continuous infusion (24.9%) versus intermittent infusion (26.8%), but the difference was not statistically significant (-1.9% difference).
Article Synopsis
- During the COVID-19 pandemic, many ICUs paused ongoing research to prioritize studies related to the virus, but the REVISE trial continued investigating stress ulcer prophylaxis in mechanically ventilated patients.
- The trial, which compares pantoprazole against a placebo, enrolled 2,961 patients across 59 centers, despite facing disruptions in enrollment during the pandemic.
- Changes in the informed consent process included a shift to a 'consent to continue' model and an increase in telephone consent due to restrictions, leading to a slight rise in overall consent rates.
Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach.
View Article and Find Full Text PDFBackground: Ascertainment of the severity of the primary outcome of upper gastrointestinal (GI) bleeding is integral to stress ulcer prophylaxis trials. This protocol outlines the adjudication process for GI bleeding events in an international trial comparing pantoprazole to placebo in critically ill patients (REVISE: Re-Evaluating the Inhibition of Stress Erosions). The primary objective of the adjudication process is to assess episodes submitted by participating sites to determine which fulfil the definition of the primary efficacy outcome of clinically important upper GI bleeding.
View Article and Find Full Text PDFArticle Synopsis
- - The study aimed to define what constitutes "patient-important" upper gastrointestinal bleeding during critical illness for a randomized trial, focusing on the perspectives of ICU survivors and their family members.
- - Using interviews and focus groups, researchers gathered qualitative data, which revealed that patient-important bleeding is linked to serious outcomes like death, disability, and extended hospital stays, along with specific medical interventions.
- - Findings highlighted that patients and families view gastrointestinal bleeding differently than traditional clinical definitions, emphasizing the context and effects of treatments as crucial to understanding its importance.
Sepsis is a common and deadly condition. Within the current model of sepsis immunobiology, the framing of dysregulated host immune responses into proinflammatory and immunosuppressive responses for the testing of novel treatments has not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalised immunomodulation.
View Article and Find Full Text PDFBACKGROUND: Trials and study-level meta-analyses have failed to resolve the role of corticosteroids in the management of patients with septic shock. Patient-level meta-analyses may provide more precise estimates of treatment effects, particularly subgroup effects. METHODS: We pooled individual patient data from septic shock trials investigating the adjunctive use of intravenous hydrocortisone.
View Article and Find Full Text PDFObjective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults.
Data Sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.
Objectives: We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for understanding sepsis pathophysiology.
Design: Retrospective multicenter cohort studies of septic shock patients.
Setting: All participants who were admitted to 27 participating hospital sites in three countries (Australia, New Zealand, and the United Kingdom) were eligible for inclusion.
Purpose: To examine the relationship of early persistent lymphopenia with hospital survival in critically ill patients with and without sepsis to assess whether it can be considered a treatable trait. Methods: Retrospective database analysis of patients with nonelective admission to intensive care units (ICUs) during January 2015 to December 2018. Patients were classified as having sepsis if the Acute Physiology and Chronic Health Evaluation III admission diagnostic code included sepsis or coded for an infection combined with a Sequential Organ Failure Assessment score of ≥2.
View Article and Find Full Text PDFBackground: The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.
Objective: To outline the statistical analysis plan for the REVISE trial.
Methods: REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally.
The Plasma-Lyte 148 versus Saline (PLUS) study is a prospective, multicentre, parallel-group, concealed, blinded, randomised controlled trial comparing the effect of Plasma-Lyte 148 versus 0.9% sodium chloride (saline) for fluid resuscitation and other fluid therapy on 90-day mortality among critically ill adults requiring fluid resuscitation. The original target for recruitment was 8800 participants, which was reduced to 5000 participants following the onset of the coronavirus disease 2019 (COVID-19) pandemic in 2020.
View Article and Find Full Text PDFTo estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales. Prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009, and followed for hospitalisation for sepsis. Incidence and hazard ratio (HR) of sepsis hospitalisation and intensive care unit (ICU) admission identified using International Classification of Diseases (10th revision) coding on discharge data.
View Article and Find Full Text PDFArticle Synopsis
- The BLING III study is a large, multi-center trial assessing the effectiveness of continuous vs. intermittent β-lactam antibiotic infusions in 7,000 critically ill sepsis patients.
- The statistical analysis plan was created by the trial's statistician and investigators, approved by the management committee, and includes detailed methods for analyzing various outcomes.
- To ensure transparency and prevent bias, the statistical plan was published before data collection was finished, with interim analyses conducted by a Data Safety and Monitoring Committee.
It remains unclear whether balanced solutions improve patient-centred outcomes in critically ill patients overall and whether the treatment effect is heterogeneous, with evidence that some populations of patients may be helped and others harmed. To provide the most up-to-date and comprehensive assessment of the totality of the evidence, we will perform an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) comparing the use of balanced solutions with saline in critically ill adults. Living systematic review using aggregated and individual patient data from randomised controlled trials.
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- The SuDDICU trial aims to evaluate the effects of selective decontamination of the digestive tract (SDD) on outcomes for ventilated patients in ICUs, focusing on whether it reduces hospital mortality and affects antibiotic resistance.
- This international study involves 19 ICUs in Australia and 10 in Canada and the UK, recruiting 15,000 to 17,000 patients over two 12-month trial periods, comparing SDD plus standard care against standard care alone.
- Key primary and secondary outcomes include all-cause hospital mortality, duration of ventilation, ICU and hospital stay, incidence of new infections, and the development of antibiotic resistance, with recruitment starting in 2017.
Background: The effect of balanced crystalloids compared with that of saline in critically ill patients overall and in specific subgroups is unclear. We aimed to assess whether use of balanced solutions, compared with 0·9% sodium chloride (saline), decreased in-hospital mortality in adult patients in intensive care units (ICUs).
Methods: For this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, and CENTRAL databases from inception until March 1, 2022 (updated Sept 1, 2023) for individually randomised and cluster-randomised trials comparing balanced solutions with saline for adult patients in the ICU.