From Traditional Typing to Intelligent Insights: A Narrative Review of Directions Toward Targeted Therapies in Delirium.

Delirium is a heterogeneous syndrome characterized by an acute change in level of consciousness that is associated with inattention and disorganized thinking. Delirium affects most critically ill patients and is associated with poor patient-oriented outcomes such as increased mortality, longer ICU and hospital length of stay, and worse long-term cognitive outcomes. The concept of delirium and its subtypes has existed since nearly the beginning of recorded medical literature, yet robust therapies have yet to be identified. Analogous to other critical illness syndromes, we suspect the lack of identified therapies stems from patient heterogeneity and prior subtyping efforts that do not capture the underlying etiology of delirium. The time has come to leverage machine learning approaches, such as supervised and unsupervised clustering, to identify clinical and pathophysiological distinct clusters of delirium that will likely respond differently to various interventions. We use sedation in the ICU as an example of how precision therapies can be applied to critically ill patients, highlighting the fact that while for some patients a sedative drug may cause delirium, in another cohort sedation is the specific treatment. Finally, we conclude with a proposition to move away from the term delirium, and rather focus on the treatable traits that may allow precision therapies to be tested.

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. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

A voice-based digital assistant for intelligent prompting of evidence-based practices during ICU rounds.

OBJECTIVE: To evaluate the technical feasibility and potential value of a digital assistant that prompts intensive care unit (ICU) rounding teams to use evidence-based practices based on analysis of their real-time discussions. METHODS: We evaluated a novel voice-based digital assistant which audio records and processes the ICU care team's rounding discussions to determine which evidence-based practices are applicable to the patient but have yet to be addressed by the team. The system would then prompt the team to consider indicated but not yet delivered practices, thereby reducing cognitive burden compared to traditional rigid rounding checklists. In a retrospective analysis, we applied automatic transcription, natural language processing, and a rule-based expert system to generate personalized prompts for each patient in 106 audio-recorded ICU rounding discussions. To assess technical feasibility, we compared the system's prompts to those created by experienced critical care nurses who directly observed rounds. To assess potential value, we also compared the system's prompts to a hypothetical paper checklist containing all evidence-based practices. RESULTS: The positive predictive value, negative predictive value, true positive rate, and true negative rate of the system's prompts were 0.45 ± 0.06, 0.83 ± 0.04, 0.68 ± 0.07, and 0.66 ± 0.04, respectively. If implemented in lieu of a paper checklist, the system would generate 56% fewer prompts per patient, with 50%±17% greater precision. CONCLUSION: A voice-based digital assistant can reduce prompts per patient compared to traditional approaches for improving evidence uptake on ICU rounds. Additional work is needed to evaluate field performance and team acceptance.

Agitation is a Common Barrier to Recovery of ICU Patients.

Importance: Agitation is common in mechanically ventilated ICU patients, but little is known about physician attitudes regarding agitation in this setting. Objectives: To characterize physician attitudes regarding agitation in mechanically ventilated ICU patients. Design, Setting, and Participants: We surveyed critical care physicians within a multicenter health system in Western Pennsylvania, assessing attitudes regarding agitation during mechanical ventilation and use of and confidence in agitation management options. We used quantitative clinical vignettes to determine whether agitation influences confidence regarding readiness for extubation. We sent our survey to 332 critical care physicians, of whom 80 (24%) responded and 69 were eligible (had cared for a mechanically ventilated patient in the preceding three months). Main Outcomes and Measures: Respondent confidence in patient readiness for extubation (0-100%, continuous) and frequency of use and confidence in management options (1-5, Likert). Results: Of 69 eligible responders, 61 (88%) agreed agitation is common and 49 (71%) agreed agitation is a barrier to extubation, but only 27 (39%) agreed their approach to agitation is evidence-based. Attitudes regarding agitation did not differ much by practice setting or physician demographics, though respondents working in medical ICUs were more likely (P = .04) and respondents trained in surgery or emergency medicine were less likely (P = .03) than others to indicate that agitation is an extubation barrier. Fifty-three (77%) respondents reported they frequently use non-pharmacologic measures to treat agitation, and 42 (70%) of those who reported they used non-pharmacologic measures during the prior 3 months indicated confidence in their effectiveness. In responses to clinical vignettes, confidence in patient's readiness for extubation was significantly lower if the patient was agitated (P < .001) or tachypneic (P < .001), but the presence of both agitation and tachypnea did not reduce confidence compared with tachypnea alone (P = .24). Conclusions and Relevance: Most critical care physicians consider agitation during mechanical ventilation a common problem and agreed that agitation is a barrier to extubation. Treatment practice varies widely.

Electroluminescence image analysis of a photovoltaic module under accelerated lifecycle testing.

Electroluminescence (EL) imaging of Si-based photovoltaic (PV) modules is used widely to spatially detect and characterize electrical defects, including handling and degradation-induced cracking of the component Si cells that are associated with reductions in module performance. In the present study, a commercial polycrystalline silicon PV module was subjected to accelerated lifecycle test environmental conditions and examined as a function of environmental exposure time using EL imaging. The approach followed pixel intensity distributions over each individual PV cell and confirmed a positive correlation between module conversion efficiency and results of the image analysis. Overall, an average of a 2.5% reduction in normalized EL intensity was correlated to a 0.35% reduction in actual power conversion efficiency (or a 2.3% decrease in relative efficiency). The imaging analysis technique offers a rapid, unsupervised means to assess EL data in lieu of conventional visual interpretation.

Platelet Bioenergetics and Associations With Delirium and Coma in Patients With Sepsis: A Prospective Cohort Study.

BACKGROUND: Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis. RESEARCH QUESTION: Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis? STUDY DESIGN AND METHODS: We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values. RESULTS: Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics. INTERPRETATION: In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.

Data-derived subtypes of delirium during critical illness.

BACKGROUND: To understand delirium heterogeneity, prior work relied on psychomotor symptoms or risk factors to identify subtypes. Data-driven approaches have used machine learning to identify biologically plausible, treatment-responsive subtypes of other acute illnesses but have not been used to examine delirium. METHODS: We conducted a secondary analysis of a large, multicenter prospective cohort study involving adults in medical or surgical ICUs with respiratory failure or shock who experienced delirium per the Confusion Assessment Method for the ICU. We used data collected before delirium diagnosis in an unsupervised latent class model to identify delirium subtypes and then compared demographics, clinical characteristics, and outcomes between subtypes in the final model. FINDINGS: The 731 patients who developed delirium during critical illness had a median age of 63 [IQR, 54-72] years, a median Sequential Organ Failure Assessment score of 8.0 [6.0-11.0] and 613 [83.4%] were mechanically ventilated at delirium identification. A four-class model best fit the data with 50% of patients in subtype (ST) 1, 18% in subtype 2, 17% in subtype 3, and 14% in subtype 4. Subtype 2-which had more shock and kidney impairment-had the highest mortality (33% [ST2] vs. 17% [ST1], 25% [ST3], and 17% [ST4], p = 0.003). Subtype 4-which received more benzodiazepines and opioids-had the longest duration of delirium (6 days [ST4] vs. 3 [ST1], 4 [ST2], and 3 days [ST3], p < 0.001) and coma (4 days [ST4] vs. 2 [ST1], 1 [ST2], and 2 days [ST3], p < 0.001). Each of the four data-derived delirium subtypes was observed within previously identified psychomotor and risk factor-based delirium subtypes. Clinically significant cognitive impairment affected all subtypes at follow-up, but its severity did not differ by subtype (3-month, p = 0.26; 12-month, p = 0.80). INTERPRETATION: The four data-derived delirium subtypes identified in this study should now be validated in independent cohorts, examined for differential treatment effects in trials, and inform mechanistic work evaluating treatment targets. FUNDING: National Institutes of Health (T32HL007820, R01AG027472).

Identifying Comorbid Subtypes of Patients With Acute Respiratory Failure.

BACKGROUND: Patients with acute respiratory failure have multiple risk factors for disability following their intensive care unit stay. Interventions to facilitate independence at hospital discharge may be more effective if personalized for patient subtypes. OBJECTIVES: To identify subtypes of patients with acute respiratory failure requiring mechanical ventilation and compare post-intensive care functional disability and intensive care unit mobility level among subtypes. METHODS: Latent class analysis was conducted in a cohort of adult medical intensive care unit patients with acute respiratory failure receiving mechanical ventilation who survived to hospital discharge. Demographic and clinical medical record data were collected early in the stay. Clinical characteristics and outcomes were compared among subtypes by using Kruskal-Wallis tests and χ2 tests of independence. RESULTS: In a cohort of 934 patients, the 6-class model provided the optimal fit. Patients in class 4 (obesity and kidney impairment) had worse functional impairment at hospital discharge than patients in classes 1 through 3. Patients in class 3 (alert patients) had the lowest magnitude of functional impairment (P < .001) and achieved the earliest out-of-bed mobility and highest mobility level of all subtypes (P < .001). CONCLUSIONS: Acute respiratory failure survivor subtypes identified from clinical data available early in the intensive care unit stay differ in post-intensive care functional disability. Future research should target high-risk patients in early rehabilitation trials in the intensive care unit. Additional investigation of contextual factors and mechanisms of disability is critical to improving quality of life in acute respiratory failure survivors.

Driving decisions after critical illness: Qualitative analysis of patient-provider reviews during ICU recovery clinic assessments.

BACKGROUND: Driving a vehicle is a functional task requiring a threshold of physical, behavioral and cognitive skills. OBJECTIVE: To report patient-provider evaluations of driving status and driving safety assessments after critical illness. DESIGN: Qualitative secondary analysis of driving-related dialog drawn from a two-arm pilot study evaluating telemedicine delivery of Intensive Care Unit Recovery Clinic assessments. Multidisciplinary providers assessed physical, psychological, and cognitive recovery during one-hour telemedicine ICU-RC assessments. Qualitative secondary analysis of patient-provider dialog specific to driving practices after critical illness. SETTING AND PATIENTS: Multidisciplinary Intensive Care Unit Recovery clinic assessment dialog between 17 patients and their providers during 3-week and/or 12-week follow-up assessments at a tertiary academic medical center in the Southeastern United States. MAIN MEASURES AND KEY RESULTS: Thematic content analysis was performed to describe and classify driving safety discussion, driving status and driving practices after critical illness. Driving-related discussions occurred with 15 of 17 participants and were clinician-initiated. When assessed, driving status varied with participants reporting independent decisions to resume driving, delay driving and cease driving after critical illness. Patient-reported driving practices after critical illness included modifications to limit driving to medical appointments, self-assessments of trip durations, and inclusion of care partners as a safety measure for new onset fatigue while driving. CONCLUSION: We found that patients are largely self-navigating this stage of recovery, making subjective decisions on driving resumption and overall driving status. These results highlight that driving status changes are an often underrecognized yet salient social cost of critical illness. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03926533.

Understanding and Managing Anxiety Sensitivity During Critical Illness and Long-Term Recovery.

Anxiety sensitivity is a fear of symptoms associated with anxiety (eg, rapid respiration and heart rate, perspiration), also known as "fear of fear." This fear is a misinterpretation of nonthreatening symptoms as threatening across 3 domains: physical ("When my heart rate increases, I'm afraid I may have a heart attack"), social ("If people see me perspire, I fear they will negatively evaluate me"), and cognitive ("When I feel these symptoms, I fear it means I'm going crazy or will lose control and do something dangerous like disconnect my IV"). These thoughts stimulate the sympathetic nervous system, resulting in stronger sensations and further catastrophic misinterpretations, which may spiral into a panic attack. Strategies to address anxiety sensitivity include pharmacologic and nonpharmacologic interventions. In intensive care unit settings, anxiety sensitivity may be related to common monitoring and interventional procedures (eg, oxygen therapy, repositioning, use of urine collection systems). Anxiety sensitivity can be a barrier to weaning from mechanical ventilation when patients are uncomfortable following instructions to perform awakening or breathing trials. Fortunately, anxiety sensitivity is a malleable trait with evidence-based intervention options. However, few health care providers are aware of this psychological construct and available treatment. This article describes the nature of anxiety sensitivity, its potential impact on intensive care, how to assess and interpret scores from validated instruments such as the Anxiety Sensitivity Index, and treatment approaches across the critical care trajectory, including long-term recovery. Implications for critical care practice and future directions are also addressed.

Measuring Performance on the ABCDEF Bundle During Interprofessional Rounds via a Nurse-Based Assessment Tool.

BACKGROUND: Nurse-led rounding checklists are a common strategy for facilitating evidence-based practice in the intensive care unit (ICU). To streamline checklist workflow, some ICUs have the nurse or another individual listen to the conversation and customize the checklist for each patient. Such customizations assume that individuals can reliably assess whether checklist items have been addressed. OBJECTIVE: To evaluate whether 1 critical care nurse can reliably assess checklist items on rounds. METHODS: Two nurses performed in-person observation of multidisciplinary ICU rounds. Using a standardized paper-based assessment tool, each nurse indicated whether 17 items related to the ABCDEF bundle were discussed during rounds. For each item, generalizability coefficients were used as a measure of reliability, with a single-rater value of 0.70 or greater considered sufficient to support its assessment by 1 nurse. RESULTS: The nurse observers assessed 118 patient discussions across 15 observation days. For 11 of 17 items (65%), the generalizability coefficient for a single rater met or exceeded the 0.70 threshold. The generalizability coefficients (95% CIs) of a single rater for key items were as follows: pain, 0.86 (0.74-0.97); delirium score, 0.74 (0.64-0.83); agitation score, 0.72 (0.33-1.00); spontaneous awakening trial, 0.67 (0.49-0.83); spontaneous breathing trial, 0.80 (0.70-0.89); mobility, 0.79 (0.69-0.87); and family (future/past) engagement, 0.82 (0.73-0.90). CONCLUSION: Using a paper-based assessment tool, a single trained critical care nurse can reliably assess the discussion of elements of the ABCDEF bundle during multidisciplinary rounds.

Patient-Level Barriers and Facilitators to Early Mobilization and the Relationship With Physical Disability Post-Intensive Care: Part 2 of an Integrative Review Through the Lens of the World Health Organization International Classification of Functioning, Disability, and Health.

BACKGROUND: Early mobilization (EM) is associated with reduced physical disability post-intensive care (PD PIC). Yet, contextual factors facilitate or impede delivery of EM in the intensive care unit (ICU). Only 45% of ICUs in the United States routinely practice EM despite its recognized benefits. OBJECTIVES: To analyze the evidence on the relationship between critical care EM, PD PIC, and personal (patient-level) factors, using the theoretical lens of the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). METHOD: The Whittemore and Knafl methodology for integrative reviews and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guidelines were followed. Qualitative, quantitative, and mixed-methods studies (n = 38) that evaluated EM and 1 or more domains of the World Health Organization ICF were included. Quality was appraised using the Mixed-Methods Appraisal Tool. Study characteristics were evaluated for common themes and relationships. The ICF domains and subdomains pertaining to each study were synthesized. RESULTS: Early mobilization delivery was influenced by personal factors. Deeper sedation level, the presence of delirium, higher patient acuity, the presence of medical devices, and patient weight were identified barriers to EM delivery. Patient engagement in EM was associated with improved delivery. Patients who enjoyed rehabilitation were more likely to demonstrate improvement in functional impairment than those who did not enjoy rehabilitation. DISCUSSION: Early mobilization is associated with reduced PD PIC, yet numerous contextual factors affect the delivery of EM in the ICU. Further study of patient-level factors and EM must explore the relationship between patient engagement, baseline demographics, and functional status at ICU admission, patient-level considerations for decisions to mobilize, and EM in the ICU. This research is critical to improving the delivery of EM in the ICU and reducing PD PIC.

Environmental Factors Affecting Early Mobilization and Physical Disability Post-Intensive Care: An Integrative Review Through the Lens of the World Health Organization International Classification of Functioning, Disability, and Health.

BACKGROUND: Early mobilization (EM) is one of few potential protective factors associated with reduced physical disability post-intensive care (PD PIC). However, only 45% of intensive care units (ICUs) in the United States routinely practice EM despite its recognized benefits. OBJECTIVES: To analyze the evidence on the relationship between critical care EM, PD PIC, and environmental factors, using the theoretical lens of the World Health Organization's (WHO's) International Classification of Functioning, Disability, and Health (ICF). METHOD: The Whittemore and Knafl methodology for integrative reviews and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines were followed. Qualitative, quantitative, and mixed-methods studies (n = 38) that evaluated EM and 1 or more domains of the WHO ICF were included. Quality was appraised using the Mixed-Methods Appraisal Tool. Study characteristics were evaluated for common themes and relationships. The ICF domains and subdomains pertaining to each study were synthesized. RESULTS: Early mobilization was related to improved functioning on the disability continuum of the WHO ICF. Early mobilization was influenced by several WHO ICF environmental factors. Dedicated physical and occupational therapy teams in the ICU, interdisciplinary rounds, and positive family and staff perception of EM facilitated intervention delivery. However, poor staffing levels, negative unit culture, perceived workload burden, and lack of equipment, education, and financial support impeded delivery of EM. DISCUSSION: Early mobilization is a promising intervention that may reduce PD PIC. However, environmental factors negatively influence delivery of EM in the ICU. Several gaps in EM research limit its acceptability in ICU practice. Existing EM research is challenged by poor methodological quality. Further study is necessary to better understand the role of EM on PD PIC and improve patient outcomes following critical illness.

Return to Driving After Critical Illness.

This cross-sectional study examines the postintensive care syndrome in patients who had vs patients who had not resumed driving 1 month after hospitalization for a critical illness.

Vacuum-ultraviolet spectroscopy of poly(methylphenylsilylene).

The first vacuum-ultraviolet spectrum of a polysilylene (chain-type polysilane) with aromatic substituents is presented. Assignments of the absorption bands of the model compound poly(methylphenylsilylene) are based on previous experimental data and theoretical electronic band structure calculations for poly(alkylsilylenes) and on ultraviolet spectra of phenyl-containing monomers and polymers. Although aryl orbitals mix with the sigma-conjugated orbitals located along the catenated silicon backbone, some transitions are largely localized on the phenyl groups. These assignments elucidate the nature of the bonding in polysilylenes and should be useful in understanding photodegradation mechanisms and in the design of related new optical materials.