A gene expression-based approach for the precision use of hydrocortisone in septic shock patients; a secondary analysis of the ADRENAL trial.

Background: Small observational studies suggest the effect of corticosteroids in patients with vasodilatory shock vary depending on endotypes determined by gene expression. We sought to replicate these findings in a larger cohort from a randomised clinical trial.

Methods: In a cross-sectional substudy of the Adjunctive Glucocorticoid Therapy In Septic Shock (ADRENAL) trial, patients were classified as one of two immune endotypes using predefined gene expression signatures: immune adaptive-prevalent (IA-P) or immune innate-prevalent (IN-P).

Accuracy of the modified Global Burden of Disease International Classification of Diseases coding methods for identifying sepsis: a prospective multicentre cohort study.

Background: This study assessed the accuracy of three International Classification of Diseases (ICD) codes methods derived from Global Burden of Disease (GBD) sepsis study (modified GBD method) in identifying sepsis, compared to the Angus method. Sources of errors in these methods were also reported.

Methods: Prospective multicentre, observational, study.

Corticosteroids for adult patients hospitalised with non-viral community-acquired pneumonia: a systematic review and meta-analysis.

Purpose: International clinical practice guidelines addressing corticosteroid treatment for patients hospitalised with non-viral community-acquired pneumonia (CAP) are inconsistent.

Methods: We conducted a systematic review of randomized controlled trials (RCTs) evaluating the use of corticosteroids in hospitalised adult patients with suspected or probable CAP. We performed random effects pairwise, Bayesian, and dose-response meta-analyses using the restricted maximum likelihood (REML) heterogeneity estimator.

Risk Factors for Patient-Important Upper Gastrointestinal Bleeding.

Patient-important gastrointestinal bleeding is an endpoint developed by patients and family members; however, risk factors for this outcome are unknown. We sought to identify risk factors for patient-important upper gastrointestinal bleeding among invasively ventilated adults. This preplanned regression analysis of an international trial database evaluated baseline and time-varying risk factors in the preceding 3 days for patient-important upper gastrointestinal bleeding, accounting for illness severity and the competing risk of death.

Buffered salt solution versus 0.9% sodium chloride as fluid therapy for patients presenting with moderate to severe diabetic ketoacidosis: Study protocol for a Phase-3 cluster-crossover, blinded, randomised, controlled trial.

Background: The optimal choice of fluid therapy for patients with diabetic ketoacidosis (DKA) is uncertain, though preliminary data suggest that buffered crystalloid solutions (Plasma-Lyte® 148) may offer some advantages over 0.9% saline.

Objective: To describe the study protocol for the 'Balanced Electrolyte Solution versus Saline Trial for Diabetic Ketoacidosis' (BEST-DKA) trial.

Serum chloride concentration and outcomes in adults receiving intravenous fluid therapy with a balanced crystalloid solution or 0.9% sodium chloride.

Purpose: To determine whether there is an interaction between baseline serum chloride concentration and pH and treatment effects in Intensive Care Unit (ICU) patients receiving intravenous fluid therapy with balanced solution versus 0.9% sodium chloride (saline).

Methods: A secondary analysis of a randomized controlled trial in which patients were divided into cohorts according to quartiles of baseline serum chloride concentration and pH.

Management of adult sepsis in resource-limited settings: global expert consensus statements using a Delphi method.

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.

Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.

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.

Performance of Risk Assessment Models for VTE in Patients Who Are Critically Ill Receiving Pharmacologic Thromboprophylaxis: A Post Hoc Analysis of the Pneumatic Compression for Preventing VTE Trial.

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.

Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding - An Updated Meta-Analysis.

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.

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

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.

From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations for Developing Precision Medicine in the ICU.

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.

Adjudication of a primary trial outcome: Results of a calibration exercise and protocol for a large international trial.

Background: 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.

Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies.

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.

Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock.

BACKGROUND: 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.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis.

Objective: 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.

A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients.

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.

EARLY PERSISTENT LYMPHOPENIA AND RISK OF DEATH IN CRITICALLY ILL PATIENTS WITH AND WITHOUT SEPSIS.

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.

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

Background: 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.