Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

Background: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes.

Systemic inflammation and delirium during critical illness.

Purpose: The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness.

Methods: In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU).

Antipsychotics and the QTc Interval During Delirium in the Intensive Care Unit: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Antipsychotic medications, often prescribed for delirium in intensive care units (ICUs), may contribute to QTc interval prolongation.

Objective: To determine whether antipsychotics increase the QTc interval in patients with delirium in the ICU.

Design, Setting, And Participants: An a priori analysis of a randomized clinical trial in medical/surgical ICUs within 16 centers across the US was conducted.

Recurrent delirium episodes within the intensive care unit: Incidence and associated factors.

Purpose: Describe the incidence and factors associated with recurrent delirium in the intensive care unit (ICU).

Materials And Methods: Retrospective study of ICU patients diagnosed with delirium. Delirium clearance defined as 48 h of negative delirium assessments following initial episode and recurrent delirium as any positive delirium assessment following clearance.

External validation of a predictive model for reintubation after cardiac surgery: A retrospective, observational study.

Study Objective: Explore validation of a model to predict patients' risk of failing extubation, to help providers make informed, data-driven decisions regarding the optimal timing of extubation.

Design: We performed temporal, geographic, and domain validations of a model for the risk of reintubation after cardiac surgery by assessing its performance on data sets from three academic medical centers, with temporal validation using data from the institution where the model was developed.

Setting: Three academic medical centers in the United States.

Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery.

Background: Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied.

Methods: This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States.

Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery : A Nationwide Cohort Study.

Background: Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time.

Objective: To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery.

In-hospital catatonia, delirium, and coma and mortality: Results from the delirium and catatonia prospective cohort investigation.

Background: Catatonia, a form of acute brain dysfunction typically linked with severe affective and psychotic disorders, occurs in critical illness with delirium and coma. Delirium and coma are associated with mortality, though catatonia's relationship with mortality is unclear. We aim to describe whether catatonia, delirium, and coma are associated with mortality.

Advancing specificity in delirium: The delirium subtyping initiative.

Background: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

Objective: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).

Background: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.

Instruments Assessing Cognitive Impairment in Survivors of Critical Illness and Reporting of Race Norms: A Systematic Review.

Unlabelled: To conduct a systematic review to summarize cognitive instruments being used in long-term outcome studies of survivors of adult critical illness, as well as evaluate whether these measures are reported as using patient demographic norms, specifically race norms.

Data Sources: A comprehensive search was conducted in PubMed (National Center for Biotechnology Information), Excerpta Medica dataBASE (Ovid), Psychological Information Database (ProQuest), and Web of Science (Clarivate) for English language studies published since 2002.

Study Selection: Studies were eligible if the population included adult ICU survivors assessed for postdischarge cognitive outcomes.

Association between cholinesterase activity and critical illness brain dysfunction.

Background: Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity.

Protocol for a randomised controlled trial: reducing reintubation among high-risk cardiac surgery patients with high-flow nasal cannula (I-CAN).

Introduction: Heated, humidified, high-flow nasal cannula oxygen therapy has been used as a therapy for hypoxic respiratory failure in numerous clinical settings. To date, limited data exist to guide appropriate use following cardiac surgery, particularly among patients at risk for experiencing reintubation. We hypothesised that postextubation treatment with high-flow nasal cannula would decrease the all-cause reintubation rate within the 48 hours following initial extubation, compared with usual care.

The genome-wide DNA methylation profiles among neurosurgery patients with and without post-operative delirium.

Aims: There is no previous study demonstrating the differences of genome-wide DNA methylation (DNAm) profiles between patients with and without postoperative delirium (POD). We aimed to discover epigenetic (DNAm) markers that are associated with POD in blood obtained from patients before and after neurosurgery.

Methods: Pre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform.

In-Hospital Depressed Level of Consciousness and Long-Term Functional Outcomes in ICU Survivors.

Objectives: Among critically ill patients, acutely depressed level of consciousness is associated with mortality, but its relationship to long-term outcomes such as disability and physical function is unknown. We investigated the relationship of level of consciousness during hospitalization with long-term disability and physical function in ICU survivors.

Design: Multi-center observational cohort study.

Design and Rationale of the Sevoflurane for Sedation in Acute Respiratory Distress Syndrome (SESAR) Randomized Controlled Trial.

Preclinical studies have shown that volatile anesthetics may have beneficial effects on injured lungs, and pilot clinical data support improved arterial oxygenation, attenuated inflammation, and decreased lung epithelial injury in patients with acute respiratory distress syndrome (ARDS) receiving inhaled sevoflurane compared to intravenous midazolam. Whether sevoflurane is effective in improving clinical outcomes among patients with ARDS is unknown, and the benefits and risks of inhaled sedation in ARDS require further evaluation. Here, we describe the SESAR (Sevoflurane for Sedation in ARDS) trial designed to address this question.

DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium.

The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed.

Delirium in critical illness: clinical manifestations, outcomes, and management.

Delirium is the most common manifestation of brain dysfunction in critically ill patients. In the intensive care unit (ICU), duration of delirium is independently predictive of excess death, length of stay, cost of care, and acquired dementia. There are numerous neurotransmitter/functional and/or injury-causing hypotheses rather than a unifying mechanism for delirium.

A Predictive Model of Reintubation After Cardiac Surgery Using the Electronic Health Record.

Background: Reintubation and prolonged intubation after cardiac surgery are associated with significant complications. Despite these competing risks, providers frequently extubate patients with limited insight into the risk of reintubation at the time of extubation. Achieving timely, successful extubation remains a significant clinical challenge.