Clinical course of patients with bloodstream infections enrolled in the BALANCE clinical trial.

Objectives: There is a lack of data describing the longitudinal clinical trajectories of vital signs and laboratory tests in patients with bloodstream infection (BSI). The BALANCE trial, which randomly assigned patients with BSI to receive 7 or 14 days of antibiotic treatment, provided rich daily data to describe these trajectories.

Methods: As part of the BALANCE trial, we collected several daily parameters (temperature, heart rate, mean arterial pressure, systolic blood pressure, respiratory rate, WBC count, C-reactive protein, platelet count and SOFA score) until Day 14 of illness, discharge or death.

Making sense of hierarchical composite endpoints in randomized clinical trials - a primer for infectious disease clinicians and researchers.

Hierarchical composite endpoints (HCEs), combining features of simple composite endpoints and conventional ordinal endpoints, are increasingly being used in infectious diseases research. However, many clinicians may be unfamiliar with these novel endpoints, including the variety of different target parameters that may be of interest and the methods that can be used to estimate them. In this review, we provide a conceptual overview of HCEs by defining them and providing examples from the infectious diseases literature.

Prehospital antibiotics and intravenous fluids for patients with sepsis: protocol for a 2×2 factorial randomised controlled trial.

Introduction: Prompt recognition and treatment of patients with sepsis improve survival. Patients transported to hospital with sepsis often do not receive treatment until they are assessed in emergency departments. Initiation of treatments by paramedics at the point of first contact may improve outcomes for these patients.

Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trial.

Background: The BALANCE trial demonstrated non-inferiority of 7 (vs 14) day antibiotic durations in patients with uncomplicated non- bacterial bloodstream infections (BSI). However, there may be patient subgroups who benefit from longer durations. We aimed to evaluate if bedside clinical decision rules could identify these subgroups.

Seven vs Fourteen Days of Antibiotics for Gram-Negative Bloodstream Infection: A Systematic Review and Noninferiority Meta-Analysis.

Importance: Gram-negative bloodstream infections are a common cause of hospitalization. A 2-week duration of antibiotic therapy has been commonly used, but shorter durations may have similar outcomes.

Objectives: To assess whether 7 days of antibiotic therapy was noninferior to 14 days.

Low-Dose Melatonin for Prevention of Delirium in Critically Ill Patients: A Multicenter, Randomized, Placebo-Controlled Feasibility Trial.

Background: Delirium is a common and serious syndrome of acute brain dysfunction associated with negative outcomes. Melatonin may have a role in delirium prevention for critically ill adults based on data from noncritically ill patient populations. Our objective was to assess the feasibility of a multicenter, randomized, placebo-controlled trial testing the hypothesis that low-dose melatonin prevents delirium in adults who are critically ill.

Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections.

Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days.

Using multi-level regression to determine associations and estimate causes and effects in clinical anesthesia due to patient, practitioner and hospital or health system practice variability.

In this research methods tutorial of clinical anesthesia, we will explore techniques to estimate the influence of a myriad of factors on patient outcomes. Big data that contain information on patients, treated by individual anesthesiologists and surgical teams, at different hospitals, have an inherent multi-level data structure (Fig. 1).

Trends in characteristics, interventions, and outcomes of hospitalized patients with COVID-19 in Canada: a multicentre prospective cohort study.

Purpose: Our objective was to investigate the temporal trends in baseline characteristics, interventions, and clinical outcomes in patients hospitalized with COVID-19 in Canada over five pandemic waves.

Methods: We conducted a multicentre prospective cohort study enrolling adults and children admitted with COVID-19 from 47 Canadian hospitals. We compared characteristics, interventions, and outcomes of patients across five distinct pandemic waves.

Sex-based Differences in the Use of Best Practices in Mechanically Ventilated Adults in the Intensive Care Unit: An Analysis of the Toronto Multicenter iCORE Database.

Patients who are critically ill and require admission to an intensive care unit (ICU) should receive the same quality of care regardless of their sex. To determine, using population data from a multicenter database in Ontario, Canada, whether sex is associated with differences in the use of eight best practices and other interventions during the ICU care of mechanically ventilated women and men. Using a cohort of patients receiving mechanical ventilation in eight ICUs, our coprimary outcomes were differences in compliance with eight evidence-based practices between women and men (opioid administration, use of continuous sedation or opioids, sedation minimization, spontaneous breathing trials, stress ulcer prophylaxis, deep venous thrombosis [DVT] prophylaxis, physical restraint, and mobilization).

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes.

Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India.

Antibiotic treatment durations for pyogenic liver abscesses: A systematic review.

Background: We sought to systematically review the existing research on pyogenic liver abscesses to determine what data exist on antibiotic treatment durations.

Methods: We conducted a systematic review and meta-analysis of contemporary medical literature from 2000 to 2020, searching for studies of pyogenic liver abscesses. The primary outcome of interest was mean antibiotic treatment duration, which we pooled by random-effects meta-analysis.

Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.

Objective: To determine whether vitamin C improves outcomes for patients with COVID-19.

Design, Setting, And Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents.

Fixed versus individualized treatment for five common bacterial infectious syndromes: a survey of the perspectives and practices of clinicians.

Background: Traditionally, bacterial infections have been treated with fixed-duration antibiotic courses; however, some have advocated for individualized durations. It is not known which approach currently predominates.

Methods: We conducted a multinational clinical practice survey asking prescribers their approach to treating skin and soft tissue infection (SSTI), community-acquired pneumonia (CAP), pyelonephritis, cholangitis and bloodstream infection (BSI) of an unknown source.

Non-inferiority trial of a shorter (7 days) compared with a longer (14 days) duration of antimicrobial therapy for the treatment of bacteraemic urinary sepsis, measured by microbiological success after the completion of therapy: a substudy protocol for the Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) multicentre randomised controlled trial.

Introduction: The BALANCE study is a randomised clinical trial (3626 participants) designed to assess the non-inferiority of 7 days (short-course) antibiotic therapy compared with 14 days of therapy for bacteraemia using the pragmatic endpoint of 90-day survival. Based on pilot study data, approximately 30% of enrolees will have a urinary tract infection (UTI) as the source of bacteraemia.

Methods And Analysis: We aim to assess the non-inferiority of short-course antibiotic therapy for patients with bacteraemia UTIs.

Does this patient have Clostridioides difficile infection? A systematic review and meta-analysis.

Background: The clinical features and predictors of Clostridioides difficile infection overlap with many conditions.

Objectives: We performed a systematic review to evaluate the diagnostic utility of clinical features (clinical examination, risk factors, laboratory tests, and radiographic findings) associated with C. difficile.

Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials.

Background: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups.

Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.

Effect of video camera monitoring feedback on hand hygiene compliance in neonatal intensive care unit, an interventional study.

Background: The purpose of this study was to determine whether use of a video camera surveillance system for hand hygiene (HH) monitoring, video-based education, and feedback could improve the HH compliance in a neonatal intensive care unit (NICU).

Methods And Materials: This was an interventional before-after trial conducted in a level-III NICU between July 2019 and June 2020. HH compliance was measured using randomly selected video-camera footage in the baseline, intervention, and maintenance periods.

Prognostic Factors Associated With Extubation Failure in Acutely Brain-Injured Patients: A Systematic Review and Meta-Analysis.

Objective: Extubation failure in brain-injured patients is associated with increased morbidity. Our objective was to systematically review prognostic factors associated with extubation failure in acutely brain-injured adult patients receiving invasive ventilation in an ICU.

Data Sources: MEDLINE, Embase, and Cochrane Central were searched from inception to January 31, 2022.

Defibrillation Strategies for Refractory Ventricular Fibrillation.

Background: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation.

Methods: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest.