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Rationale: Delirium is a frequent occurrence in older intensive care unit (ICU) patients, but the importance of the duration of delirium in contributing to adverse long-term outcomes is unclear.Objectives: To examine the association of the number of days of ICU delirium with mortality in an older patient population.Methods: We performed a prospective cohort study in a 14-bed ICU in an urban acute care hospital. The patient population comprised 304 consecutive admissions 60 years of age and older.Measurements and Main Results: The main outcome was 1-year mortality after ICU admission. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a validated chart review method. The median duration of ICU delirium was 3 days (range, 1-46 d). During the follow-up period, 153 (50%) patients died. After adjusting for relevant covariates, including age, severity of illness, comorbid conditions, psychoactive medication use, and baseline cognitive and functional status, the number of days of ICU delirium was significantly associated with time to death within 1 year post-ICU admission (hazard ratio, 1.10; 95% confidence interval, 1.02-1.18).Conclusions: Number of days of ICU delirium was associated with higher 1-year mortality after adjustment for relevant covariates in an older ICU population. Investigations should be undertaken to reduce the number of days of ICU delirium and to study the impact of this reduction on important health outcomes, including mortality and functional and cognitive status. [ABSTRACT FROM AUTHOR]

People over age 65 are the fastest growing segment of the population and account for 42% to 52% of the intensive care unit admissions in the United States. There are many physiologic changes that occur with aging which can impact on both the presentation and management of older patients with critical illness. Older patients have an increased risk for the development of sepsis, and age itself impacts on outcomes related to sepsis. Delirium is also very prevalent among older intensive care unit patients and is associated with adverse outcomes. While outcome studies suggest that chronologic age itself is not a risk factor for poor outcomes after adjusting for severity of illness, older patients clearly have physiologic changes which need to be considered when providing critical care. This article will review important physiologic changes of aging, as well as sepsis and delirium and outcomes of older ICU patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of dementia on the outcomes of intensive care unit (ICU) care and use of ICU interventions among older patients.Design: Prospective observational cohort study.Setting: Urban university teaching hospital.Patients: Patients were 395 patients age >/=65 consecutively admitted to a medical ICU.Interventions: None.Measurements and Main Results: Dementia was determined by a previously validated proxy measure, the Modified Blessed Dementia Rating Scale. We chose cut points to focus on patients with moderate-severe dementia at baseline. Our primary outcomes included length of mechanical ventilation and ICU and hospital length of stay. Secondary outcomes included ICU readmission, changes in code status, discharge location, mortality, and use of ICU interventions. Medical record abstraction was performed to determine the rates of ICU outcomes, use of ICU interventions, and potential confounders. Our study documented a prevalence of moderate-severe dementia of 17% in patients age >/=65 admitted to the ICU. Patients with dementia were significantly older (80 vs. 76), more likely to be female (65% vs. 52%), and more likely to be admitted from a nursing home (46% vs. 11%). Patients with dementia had significantly higher Acute Physiology and Chronic Health Evaluation II scores on admission to the ICU (25 vs. 23). Patients with dementia were more likely to have their code status changed to less aggressive in the ICU (24% vs. 14%). There was no significant difference in readmission to the ICU, discharge location, ICU or hospital mortality rate, or use of ICU interventions between patients with and without dementia.Conclusions: Our study documents no difference in outcomes from ICU care in older patients with and without dementia. There was no increased short-term mortality rate in older patients with dementia compared with those without dementia after admission to the ICU. Presumptions that outcomes from critical care are less favorable in patients with dementia should not drive treatment decisions in the ICU. [ABSTRACT FROM AUTHOR]

A method to measure the real time temperature distribution along an interferometer path based on the propagation of acoustic waves is presented. It exploits the high sensitivity of the speed of sound in air to the air temperature. In particular, it takes advantage of a special set-up where the generation of the acoustic waves is synchronous with the amplitude modulation of a laser source. A photodetector converts the laser light to an electronic signal considered as reference, while the incoming acoustic waves are focused on a microphone and generate a second signal. In this condition, the phase difference between the two signals substantially depends on the temperature of the air volume interposed between the sources and the receivers. The comparison with the traditional temperature sensors highlighted the limit of the latter in case of fast temperature variations and the advantage of a measurement integrated along the optical path instead of a sampling measurement. The capability of the acoustic method to compensate the interferometric distance measurements due to air temperature variations has been demonstrated for distances up to 27 m.

Abstract Background Accurate measurement of quality of life in older ICU survivors is difficult but critical for understanding the long-term impact of our treatments. Activities of daily living (ADLs) are important components of functional status and more easily measured than quality of life (QOL). We sought to determine the cross-sectional associations between disability in ADLs and QOL as measured by version one of the Short Form 12-item Health Survey (SF-12) at both one month and one year post-ICU discharge. Methods Data was prospectively collected on 309 patients over age 60 admitted to the Yale-New Haven Hospital Medical ICU between 2002 and 2004. Among survivors an assessment of ADL's and QOL was performed at one month and one-year post-ICU discharge. The SF-12 was scored using the version one norm based scoring with 1990 population norms. Multivariable regression was used to adjust the association between ADLs and QOL for important covariates. Results Our analysis of SF-12 data from 110 patients at one month post-ICU discharge showed that depression and ADL disability were associated with decreased QOL. Our model accounted for 17% of variability in SF12 physical scores (PCS) and 20% of variability in SF12 mental scores (MCS). The mean PCS of 37 was significantly lower than the population mean whereas the mean MCS score of 51 was similar to the population mean. At one year mean PCS scores improved and ADL disability was no longer significantly associated with QOL. Mortality was 17% (53 patients) at ICU discharge, 26% (79 patients) at hospital discharge, 33% (105 patients) at one month post ICU admission, and was 45% (138 patients) at one year post ICU discharge. Conclusions In our population of older ICU survivors, disability in ADLs was associated with reduced QOL as measured by the SF-12 at one month but not at one year. Although better markers of QOL in ICU survivors are needed, ADLs are a readily observable outcome. In the meantime, clinicians must try to offer realistic estimates of prognosis based on available data and resources are needed to assist ICU survivors with impaired ADLs who wish to maintain their independence. More aggressive diagnosis and treatment of depression in this population should also be explored as an intervention to improve quality of life.

Abstract Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function.

Competing Interests: Financial/Nonfinancial Disclosures None declared.

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., Methods: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete., Findings: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo., Interpretation: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults., Funding: National Institutes of Health and the US Department of Veterans Affairs., Competing Interests: Declaration of interests The following declarations of interest are reported outside of the submitted work. MFM reports grants from the National Institutes of Health (NIH) and the US Department of Veterans Affairs. LMB reports grants from the NIH and the American Association of Critical Care Nurses. MNG reports grants from the NIH, the Agency for Healthcare Research and Quality, and the US Centers for Disease Control and Prevention; consulting fees for a role as scientific advisor for Endpoint Health; honoraria for grand rounds presentation at Yale University (New Haven, CT, USA); travel support from the American Thoracic Society executive committee; and participation on the data safety monitoring board for a trial on monoclonal antibodies for COVID-19, funded by Regeneron (NCT04452318). AM reports consulting fees from Zoll, Eli Lilly, LivaNova, and Jazz Pharmaceuticals; and a philanthropic contribution from ResMed to the University of California San Diego (La Jolla, CA, USA). BAK reports grants from the NIH, payment for expert testimony for a medicolegal case in the state of Indiana (USA), payment for participation on a data safety monitoring board for the PANDORA trial, and a leadership role as president of the American Delirium Society. SSC reports grants from the NIH and direct payments for participation on the data safety monitoring board of an NIH-funded study unrelated to delirium. CLH reports grants from the NIH. PR reports grants from the NIH and the US Department of Defense, payment and travel support for a continuing medical education event at the Johns Hopkins School of Medicine, and previous leadership of the Association of Academic Anesthesiology Chairs and Society of Academic Associations of Anesthesiology and Perioperative Medicine. BTP reports leadership as co-chair of the Society of Critical Care Medicine ICU Liberation Committee. PPP reports grants from the NIH. NEB reports grants from the NIH and travel support for the Society of Intensive Care Medicine Singapore annual meeting. CGH reports consulting fees for Sedana Medical. MBP reports grants from CSL Behring, the NIH, and the US Department of Defense; royalties for serving as an associate editor with Elsevier on a surgical textbook; travel support for continuing medical education events with the Eastern Association for the Surgery of Trauma, Society of University Surgeons, and American College of Surgeons; a patent for image-derived prognostic models unrelated to this work; participation on a data safety monitoring board for Liberate Medical; and leadership as treasurer for the Eastern Association for the Surgery of Trauma. JLS reports honoria for presentations for the Society of Critical Care Medicine, American College of Chest Physicians, the Chilean Society of Critical Care Medicine, and the Spanish Society of Hospital Pharmacy; travel support for meetings with the Society of Critical Care Medicine, the Saudi Society of Clinical Pharmacy, and the Chilean Society of Critical Care Medicine; and leadership on committees with the Society of Critical Care Medicine. EWE reports grant support from the NIH and the US Department of Veterans Affairs, honoraria for continuing medical education lectures sponsored by Pfizer, and study support (investigational drug provision, no direct payments) from Eli Lilly. TDG reports grants from the NIH, research funding from Ceribell, and personal fees from Haisco Pharmaceutical and Lungpacer Medical. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type., Results: The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type., Conclusions: The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs., (© 2023 The American Geriatrics Society.)

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., Design: Retrospective cohort study., Setting: U.S. hospitals in the Premier Healthcare Database., Patients: 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018., Interventions: Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg)., Measurements: The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting., Results: The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group., Limitation: Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment., Conclusion: These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3021.

Background: People aging with and without HIV (PWH and PWoH) want to avoid neurocognitive dysfunction, especially delirium. Continued use of alcohol in conjunction with neurocognitively active medications (NCAMs) may be a largely underappreciated cause, especially for PWH who experience polypharmacy a decade earlier than PWoH. We compare absolute and relative risk of delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs., Methods: Using the VACS cohort, we compare absolute and relative risk of inpatient delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs between 2007 and 2019. We matched each case based on age, race/ethnicity, sex, HIV, baseline year, and observation time with up to 5 controls. The case/control date was defined as date of admission for cases and the date corresponding to the same length of time on study for controls. Level of alcohol use was defined using Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Medication exposure was measured from 45 to 3 days prior to index date; medications were classified as anticholinergic NCAM, non-anticholinergic NCAM, or non NCAM and counts generated. We used logistic regression to determine odds ratios (ORs) for delirium associated with medication counts stratified by HIV status and adjusted for demographics, severity of illness, and related diagnoses., Results: PWH experienced a higher incidence of delirium (5.6, [95% CI 5.3-5.9/1000 PY]) than PWoH (5.0, [95% CI 4.8-5.1/1000 PY]). In multivariable analysis, anticholinergic and non-anticholinergic NCAM counts and level of alcohol use demonstrated strong independent dose-response associations with delirium., Conclusions: Decreasing alcohol use and limiting the use of neurocognitively active medications may help decrease excess rates of delirium, especially among PWH., (© 2023 The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Mechanically ventilated patients experience many adverse symptoms, such as anxiety, thirst, and dyspnea. However, these common symptoms are not included in practice guideline recommendations for routine assessment of mechanically ventilated patients. An American Thoracic Society-sponsored workshop with researchers and clinicians with expertise in critical care and symptom management was convened for a discussion of symptom assessment in mechanically ventilated patients. Members included nurses, physicians, a respiratory therapist, a speech-language pathologist, a critical care pharmacist, and a former intensive care unit patient. This report summarizes existing evidence and consensus among workshop participants regarding 1 ) symptoms that should be considered for routine assessment of adult patients receiving mechanical ventilation; 2 ) key symptom assessment principles; 3 ) strategies that support symptom assessment in nonvocal patients; and 4 ) areas for future clinical practice development and research. Systematic patient-centered assessment of multiple symptoms has great potential to minimize patient distress and improve the patient experience. A culture shift is necessary to promote ongoing holistic symptom assessment with valid and reliable instruments. This report represents our workgroup consensus on symptom assessment for mechanically ventilated patients. Future work should address how holistic, patient-centered symptom assessment can be embedded into clinical practice.

Background: Nicotine replacement therapy, bupropion, and varenicline are smoking cessation medications (SCMs) shown to be similarly effective in people with and without human immunodeficiency virus (PWH and PWoH, respectively), although rates of receipt of these medications are unknown., Methods: We identified patients in the Veterans Aging Cohort Study with electronic health record-documented current smoking using clinical reminder data for tobacco use (2003-2018). We measured receipt of SCMs using Veterans Affairs pharmacy data for outpatient prescriptions filled 0-365 days after current smoking documentation. We used log-linear, Poisson-modified regression models to evaluate the relative risk (RR) for receiving SCM by human immunodeficiency virus (HIV) status, the annual rate of receipt, and rate difference among PWH relative to PWoH., Results: The sample included 92 632 patients (29 086 PWH), reflecting 381 637 documentations of current smoking. From 2003 to 2018, the proportion receiving SCMs increased from 15% to 34% for PWH and from 17% to 32% among PWoH. There was no statistical difference in likelihood of receiving SCM by HIV status (RR, 1.010; 95% confidence interval [CI], .994-1.026). Annual rates of receiving SCM increased for PWH by 4.3% per year (RR, 1.043; 95% CI, 1.040-1.047) and for PWoH by 3.7% per year (RR, 1.037; 95% CI, 1.036-1.038; rate difference +0.6% [RR, 1.006; 95% CI, 1.004-1.009])., Conclusions: In a national sample of current smokers, receipt of SCM doubled over the 16-year period, and differences by HIV status were modest. However, fewer than 35% of current smokers receive SCM annually. Efforts to improve SCM receipt should continue for both groups given the known dangers of smoking., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Existing assessment tools for competence in critical care ultrasound (CCUS) have limited scope and interrupt clinical workflow. The framework of entrustable professional activities (EPAs) is well suited to developing an assessment tool that is comprehensive and readily integrated into the intensive care unit (ICU) training environment., Objective: This study sought to design an EPA-based tool to assess competence in CCUS for pulmonary and critical care fellows and to assess the validity and reliability of the tool., Methods: Eight experts in CCUS met to define the core EPAs for CCUS. A nominal group technique was used to reach consensus. An assessment tool was created based on the EPAs with a modified Ottawa entrustability scale. Trained faculty evaluated pulmonary and critical care fellows using this tool in the ICU over a 6-month study period at a single institution. An assessment of validity of the EPA-based tool is made with four sources of validity evidence: content, response process, reliability, and relation to other variables. Reliability and response process data were generated using generalizability theory analysis to estimate sources of variance in entrustment scores. Analysis of response process validity and validity by relation to other variables was performed using regression models., Results: Fifty-four assessments were recorded during the study period, conducted on 23 trainees by 13 faculty. Content validity of the tool was demonstrated using expert consensus and published guidelines from critical care societies to define the EPAs. Response process validity was demonstrated by the low variance in entrustment scores due to evaluators (0.086 or 6%) and high agreement between score and trainee self-assessment (regression coefficient, 0.82; P  < 0.0001). Reliability was demonstrated by the high "true" variance in entrustment score attributable to the trainee: 0.674 or 45%. Validity by relation to other variables was demonstrated using regression analysis to show correlation between entrustment score and the number of times a fellow has performed an EPA (regression coefficient, 0.023; P  < 0.0001)., Conclusion: An EPA-based assessment tool for competence in CCUS was created. We obtained sufficient validity evidence on three of the diagnostic EPAs. Procedural EPAs were infrequently assessed, limiting generalizability in this subgroup., (Copyright © 2023 by the American Thoracic Society.)

Background: Critical illness often leads to persistent functional impairment among older Intensive Care Unit (ICU) survivors. Identification of high-risk survivors prior to discharge from their ICU hospitalization can facilitate targeting for restorative interventions after discharge, potentially improving the likelihood of functional recovery. Our objective was to develop and validate a prediction model for persistent functional impairment among older adults in the year after an ICU hospitalization., Methods: The analytic sample included community-living participants enrolled in the National Health and Aging Trends Study 2011 cohort who survived an ICU hospitalization through December 2017 and had a follow-up interview within 1 year. Persistent functional impairment was defined as failure to recover to the pre-ICU level of function within 12 months of discharge from an ICU hospitalization. We used Bayesian model averaging to identify the final predictors from a comprehensive set of 17 factors. Discrimination and calibration were assessed using area-under-the-curve (AUC) and calibration plots., Results: The development cohort included 456 ICU admissions (2,654,685 survey-weighted admissions) and the validation cohort included 227 ICU admissions (1,350,082 survey-weighted admissions). In the development cohort, the median age was 81.0 years (interquartile range [IQR] 76.0, 86.0) and 231 (50.7%) participants were women; demographic characteristics were comparable in the validation cohort. The rates of persistent functional impairment were 49.3% (development) and 50.2% (validation). The final model included age, pre-ICU disability, probable dementia, frailty, prior hospitalizations, vision impairment, depressive symptoms, and hospital length of stay. The model demonstrated good discrimination (AUC 71%, 95% confidence interval [CI] 0.66-0.76) and good calibration. When applied to the validation cohort, the model demonstrated comparable discrimination (AUC 72%, 95% CI 0.66-0.78) and good calibration., Conclusions: Application of the model prior to discharge from an ICU hospitalization may identify older adults at the highest risk of persistent functional impairment in the subsequent year, thereby facilitating targeted interventions and follow-up., (© 2022 The American Geriatrics Society.)

Purpose: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU)., Methods: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities., Results: The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia"., Conclusion: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

The cosinor model, in which a cosine curve is fitted to periodic data within a regression model, is a frequently used method for describing patterns of cyclical activity such as circadian rhythms. For circadian variables of interest (eg, melatonin and heart rate) that do not take on negative values, the assumption of normally distributed residuals required by the general linear model, which is most commonly used for cosinor analysis, may not be appropriate. Alternatively, a generalized linear model with the gamma distribution (GZLM-gamma) is specifically defined to accommodate non-negative outcomes. Herein, we demonstrate the improved fit and gains of efficiency in detection of circadian rhythm afforded by using the GZLM-gamma in cosinor models of heart rate, actigraphic activity, and urinary 6-sulfatoxymelatonin. Notably, this improved detection of circadian rhythm allows retention of additional patients for downstream analyses, further improving study power., (Copyright © 2022. Published by Elsevier B.V.)

Limited deflection of structural members represents an important requirement to guarantee proper functionality and appearance of building and infrastructures. According to Eurocodes, this requirement is ensured by limiting the maximum deflection of horizontal structural members to a fraction of their span. However, each Eurocode provides different maximum deflection limits, which are independent of the type of superstructures considered. Thus, the respect of these limits may not always guarantee the integrity of certain superstructures. In this paper, the reliability of the Eurocode deflection control methods, in guaranteeing the integrity of the superstructures, is assessed and discussed. First, different types of horizontal member, namely rib and clay (hollow) pot, composite steel-concrete, and timber beam slabs are designed to respect the deflection limit enforced by the Eurocodes. Then, the maximum curvature developed by these members is compared with the ultimate (limit) curvatures of various superstructures (e.g., ceramic and stone tile floorings). The results obtained show that the approach adopted by Eurocode 2 may provide non-conservative results, but also that the rules proposed by Eurocodes 4 and 5, albeit more reliable, do not always guarantee the integrity of the superstructure. Based on these results, an alternative method, based on the curvature control, is proposed and its advantages and limitations critically discussed. This method appears simpler and more reliable than the method currently adopted by the Eurocodes.

Rehabilitation, strengthening, and retrofitting of existing masonry buildings represent an important challenge for the construction engineering field. Often, slab strengthening/retrofitting is performed by replacing existing timber and steel beams or by adding new beams to improve the slab load-carrying capacity. The computation of the stresses at the beam-masonry interface (i.e., the contact pressure) is crucial to properly design the beam support length, preventing local failure of masonry and beam. This paper presents a simple analytical procedure to compute the contact pressure at the beam-masonry interface. The analytical procedure is validated by comparison between analytical and corresponding numerical results obtained by finite element modeling. Different types of beam (solid and laminated timber beams and steel beams) were considered, as well as different support conditions (simply resting on the wall considering different support lengths or fully embedded). The results obtained show that the method proposed is simple and reliable, which makes it suitable for professional practice.

Background: People with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count., Setting: We studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015., Methods: Primary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200-349; 50-199; <50), comorbidity and prior healthcare utilization using proportional hazards models. We also adjusted for severity of illness using discharge VACS Index (VI) 2.0 among VA-based survivors., Results: In adjusted models, CD4+ categories <350 cells/μl were associated with increased risk for both outcomes up to 6 months, and risk increased with lower CD4+ categories (e.g. 6-month mortality CD4+ 200-349 hazard ratio [HR] = 1.35 [1.12-1.63]; CD4+ <50 HR = 2.14 [1.72-2.66]); unsuppressed status was not associated with outcomes. After adjusting for VI in models stratified by HIV, VI quintiles were strongly associated with both outcomes at both time points., Conclusion: PWH who survive MICU admissions are at increased risk for worse outcomes compared with uninfected, especially those without CD4+ cell recovery. Severity of illness at discharge is the strongest predictor for outcomes regardless of HIV status. Strategies including intensive case management for HIV-specific and general organ dysfunction may improve outcomes for MICU survivors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Cosinor analysis, developed by Franz Hallberg and colleagues in the 1960s, allows for the fitting of a cosine curve to data of a known period. Cosinor analysis is frequently used in the analysis of biological rhythm data. While software exists to perform these analyses, we are not aware of any published SAS procedures or macros which would facilitate them., Methods: To meet this gap, we herein describe SAS macros which perform cosinor analyses that assume either normally or gamma distributed outcomes and fixed period. The macros can 1) produce datasets with cosinor parameters including acrophase, mesor, amplitude, nadir and test for rhythmicity 2) output datasets with fitted and observed values from the model, and 3) plot the resulting curve and underlying data., Results: We demonstrate the use of these macros with data from our research on circadian rhythms of heart rate and sleep in critically ill patients., Conclusions: Cosinor analysis provides a parsimonious and intuitive set of estimates to summarize periodic data. We are hopeful that the publication of our macro will allow a wider spectrum of users to avail themselves of this technique., Competing Interests: Declaration of Competing Interest We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with its submission. We have no conflicts of interest to disclose, (Copyright © 2021. Published by Elsevier B.V.)

Disparities in health care have risen to the forefront of medicine in the past several years. One of the most notable disparities in the research and delivery of health care relates to sex and gender. Sex and gender affect the epidemiology, pathophysiology, and outcomes of disease and social determinants of health and access to medical care. This article discusses some of the history of considering sex as a biologic variable in medical research and clinical care. It also clarifies the definitions and terminology necessary for understanding the biologic and social underpinnings of sex and gender., Competing Interests: Disclosure Dr S. Kay and Dr M.A. Pisani have no commercial or financial conflicts of interest with this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Purpose: To determine whether obstructive sleep apnea (OSA) is associated with intracerebral hemorrhage (ICH) risk, we assessed premorbid OSA exposure of patients with nontraumatic ICH and matched controls., Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage is a multicenter, case-control study evaluating risk factors for ICH that recruited 3000 cases with ICH and 3000 controls. OSA status was ascertained using the Berlin Questionnaire as a surrogate for premorbid OSA. We performed logistic regression analyses to evaluate the association between OSA and ICH., Results: Two thousand and sixty-four (71%) cases and 1516 (52%) controls were classified as having OSA by the Berlin Questionnaire. Cases with OSA were significantly more likely to be male and have hypertension, heart disease, hyperlipidemia, and higher body mass index compared with those without OSA. OSA was more common among cases compared with controls (71% versus 52%, odds ratio, 2.28 [95% CI, 2.05-2.55]). In a multivariable logistic regression model, OSA was associated with increased risk for ICH (odds ratio, 1.47 [95% CI, 1.29-1.67])., Conclusions: OSA is a risk factor for ICH.

Circadian disruption is common in critically ill patients admitted to the intensive care unit (ICU). Understanding and treating circadian disruption in critical illness has significant potential to improve critical illness outcomes through improved cognitive, immune, cardiovascular, and metabolic function. Measurement of circadian alignment (i.e., circadian phase) can be resource-intensive as it requires frequent blood or urine sampling over 24 or more hours. Less cumbersome methods of assessing circadian alignment would advance investigations in this field. Thus, the objective of this study is to examine the feasibility of using continuous telemetry to assess diurnal variation in heart rate (HR) among medical ICU patients as a proxy for circadian alignment. In exploratory analyses, we tested for associations between misalignment of diurnal variation in HR and death during hospital admission. This was a prospective observational cohort study embedded within a prospective medical ICU biorepository. HR data were continuously collected (every 5 s) via telemetry systems for the duration of the medical ICU admission; the first 24 h of this data was analyzed. Patients were extensively characterized via medical record chart abstraction and patient interviews. Of the 56 patients with complete HR data, 48 (86%) had a detectable diurnal variation. Of these patients with diurnal variation, 39 (81%) were characterized as having the nadir of their HR outside of the normal range of 02:00-06:00 ("misalignment"). Interestingly, no deaths occurred in the patients with normally aligned diurnal variation; in contrast, there were seven deaths (out of 39 patients) in patients who had misaligned diurnal variation in HR. In an exploratory analysis, we found that the odds ratio of death for misaligned vs. aligned patients was increased at 4.38; however, this difference was not statistically significant (95% confidence interval 0.20-97.63). We conclude that diurnal variation in HR can be detected via continuous telemetric monitoring of critically ill patients. A majority of these patients with diurnal variation exhibited misalignment in their first 24 h of medical ICU admission. Exploratory analyses suggest possible associations between misalignment and death., (Copyright © 2020 Knauert, Murphy, Doyle, Pisani, Redeker and Yaggi.)

Sleep is important to health and well-being, and studies in healthy adults have demonstrated that sleep deprivation impacts respiratory, immune, and cognitive function. Historically, because of the nature of critical illness, sleep has not been considered a priority for patient care in the ICU. More recently, research has demonstrated that sleep is markedly abnormal in patients who are critically ill. In addition, there is often disruption of circadian rhythms. Delirium is a syndrome of acute alteration in mental status that occurs in the setting of contributing factors such as serious illness, medication, and drug or alcohol intoxication or withdrawal. Delirium is a frequent occurrence in critical illness, and research has demonstrated several adverse outcomes associated with delirium including persistent cognitive impairment and increased mortality. Sleep deprivation and delirium share many common symptoms. The similarity in symptoms between sleep disruption and delirium have prompted experts to draw links between the two and question both the relationship and its direction. In addition, the inclusion of sleep disturbance to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition in its constellation of symptoms used in diagnosing delirium has increased awareness of the link between sleep and delirium. This paper will review the literature on sleep in critical illness and the potential mechanisms and pathways that may connect sleep and delirium., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) has a high diagnostic yield when evaluating mediastinal and hilar lymphadenopathy (LAD). Having previously demonstrated the safety of EBUS-guided cautery-assisted transbronchial nodal forceps biopsy (ca-TBFB), we report disease-specific improvements in diagnostic yield and tissue acquisition when supplementing the EBUS-TBNA-based standard of care (SOC) with ca-TBFB., Methods: We retrospectively reviewed 213 patients who sequentially underwent SOC and ca-TBFB during the same procedure. We determined 3 clinical scenarios of interest based on preprocedural imaging: isolated mediastinal/hilar LAD, LAD associated with a nodule or mass suspicious for malignancy, and LAD associated with parenchymal findings suggestive of sarcoidosis. Using validated methods, we assessed diagnostic yield on a per-patient basis and specimen quality on a per-node basis on the 136 patients meeting diagnostic criteria., Results: Administration of disease-specific SOC with ca-TBFB yielded gains that varied by diagnosis. Diagnostic yields of SOC and its supplementation with ca-TBFB were 91.8% and 93.4% (P = .50) of the 61 patients diagnosed with solid-organ malignancy, 62.7% and 94.9% (P < .001) of the 59 patients diagnosed with sarcoidosis, and 62.5% and 93.8% (P = .042) of the 16 patients diagnosed with lymphoma, the. For each disease process, specimens obtained with ca-TBFB exhibited statistically higher quality., Conclusions: We suggest that relative to SOC, ca-TBFB improves diagnostic yield for sarcoidosis and lymphoma while providing uniformly better tissue quality and cellularity. We propose a protocol for use of this innovative technique., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Smoking is highly prevalent among people living with HIV (PLWH) and increases cardiovascular risk. Pharmacotherapies such as nicotine replacement therapy (NRT), bupropion, and varenicline help to reduce smoking, though rates of receipt among PLWH compared with HIV-uninfected persons are unknown. Among 814 PLWH and 908 uninfected patients enrolled in the Veterans Aging Cohort Study (2012-2017) who reported current smoking, we used marginal multivariable log-linear regression models to estimate adjusted relative risks (ARR) of receiving pharmacotherapy by HIV status. We also assessed patient-level factors associated with pharmacotherapy receipt within each group. In multivariable analyses, receipt of NRT was less likely among PLWH relative to uninfected participants (ARR 0.77, 95% CI 0.67, 0.89). In both populations, documented mental health disorders and contemplation to quit were associated with greater likelihood of receiving pharmacotherapy. Further research is needed to explore potential treatment disparities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients undergoing thoracentesis often have comorbid conditions or take medications that potentially put them at higher bleeding risk. Direct oral anticoagulant (DOAC) use has also increased significantly. There are no published guidelines or consensus on when to perform thoracentesis in patients on anticoagulants. Recent studies support the safety of a more liberal approach for thoracentesis among patients with coagulopathy., Methods: We conducted a survey to ascertain the practices of physicians regarding thoracentesis in patients with increased bleeding risk. The survey was administered to the email distribution lists of the American Association of Bronchology and Interventional Pulmonology and of the American Thoracic Society., Results: The survey was completed by 256 attending physicians. Most of them were general pulmonologists practicing at academic medical centers. Most of them would perform a thoracentesis in patients receiving acetylsalicylic acid or prophylactic doses of unfractionated heparin or low molecular weight heparin (96%, 89%, and 88%, respectively). Half of the respondents would perform a thoracentesis in patients on antiplatelet medications (clopidogrel and ticagrelor, 51%; ticlopidine, 53%). A minority would perform thoracentesis in patients on direct oral anticoagulants or infused thrombin inhibitors (19% and 12%, respectively). The only subgroup that had a higher proclivity for performing thoracentesis without holding medications were attending physicians practicing for under 10 years. Relative to noninterventional pulmonologists, there were no significant differences in the responses of interventional pulmonologists., Conclusion: There was variation in the practice patterns of attending physicians in performing thoracentesis in patients with elevated bleeding risk. Further data and guidelines regarding the safety of thoracentesis in these patients are needed.

Objectives: One goal of early mobilization programs is to facilitate discharge home after an ICU hospitalization, but little is known about which factors are associated with this outcome. Our objective was to evaluate factors associated with discharge home among medical ICU patients in an early mobilization program who were admitted to the hospital from home., Design: Retrospective cohort study of medical ICU patients in an early mobilization program., Setting: Tertiary care center medical ICU., Patients: Medical ICU patients receiving early mobilization who were community-dwelling prior to admission., Interventions: None., Measurements and Main Results: A comprehensive set of baseline, ICU-related, and mobilization-related factors were tested for their association with discharge home using multivariable logistic regression. Among the analytic cohort ( n = 183), the mean age was 61.9 years (sd 16.67 yr) and the mean Acute Physiology and Chronic Health Evaluation II score was 23.5 (sd 7.11). Overall, 65.0% of patients were discharged home after their critical illness. In multivariable analysis, each incremental increase in the maximum level of mobility achieved (range, 1-6) during the medical ICU stay was associated with nearly a 50% greater odds of discharge home (odds ratio, 1.46; 95% CI, 1.13-1.88), whereas increased age (odds ratio, 0.95; 95% CI, 0.93-0.98) and greater hospital length of stay (odds ratio, 0.94; 95% CI, 0.90-0.99) were associated with decreased odds of discharge home. Prehospital ambulatory status was not associated with discharge home., Conclusions: Among medical ICU patients who resided at home prior to their ICU admission, the maximum level of mobility achieved in the medical ICU was the factor most strongly associated with discharge back home. Identification of this factor upon ICU-to-ward transfer may help target mobilization plans on the ward to facilitate a goal of discharge home., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Managing pain and delirium are crucial to patients, families, and caregivers in intensive care units. The Society of Critical Care Medicine 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep disruption (PADIS) guidelines reviewed literature until October 2015 and made its recommendations for critically-ill adults. This chapter addresses evidence gaps, identified during the guideline process, most relevant to clinicians, adds newer evidence published after the PADIS 2018 guidelines were produced, describes hindsight-driven PADIS process or content-related gaps, and reflects on how these considerations may help inform future research investigations and new guideline efforts., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: Our purpose was to create a content domain framework for delirium severity to inform item development for a new instrument to measure delirium severity., Methods: We used an established, multi-stage instrument development process during which expert panelists discussed best approaches to measure delirium severity and identified related content domains. We conducted this work as part of the Better ASsessment of ILlness (BASIL) study, a prospective, observational study aimed at developing and testing measures of delirium severity. Our interdisciplinary expert panel consisted of twelve national delirium experts and four expert members of the core research group. Over a one-month period, experts participated in two rounds of review., Results: Experts recommended that the construct of delirium severity should reflect both the phenomena and the impact of delirium to create an accurate, patient-centered instrument useful to interdisciplinary clinicians and family caregivers. Final content domains were Cognitive, Level of consciousness, Inattention, Psychiatric-Behavioral, Emotional dysregulation, Psychomotor features, and Functional. Themes debated by experts included reconciling clinical geriatrics and psychiatric content, mapping symptoms to one specific domain, and accurate capture of unclear clinical presentations., Conclusions: We believe this work represents the first application of instrument development science to delirium. The identified content domains are inclusive of various, wide-ranging domains of delirium severity and are reflective of a consistent framework that relates delirium severity to potential clinical outcomes. Our content domain framework provides a foundation for development of delirium severity instruments that can help improve care and quality of life for patients with delirium.

Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pleural effusions may be aspirated manually or via vacuum during thoracentesis. This study compares the safety, pain level, and time involved in these techniques., Methods: We randomized 100 patients receiving ultrasound-guided unilateral thoracentesis in an academic medical center from December 2015 through September 2017 to either vacuum or manual drainage. Without using pleural manometry, the effusion was drained completely or until the development of refractory symptoms. Measurements included self-reported pain before and during the procedure (from 0 to 10), time for completion of drainage, and volume removed. Primary outcomes were rates of all-cause complications and of early termination of the procedure with secondary outcomes of change in pain score, drainage time, volume removed, and inverse rate of removal., Results: Patient characteristics in the manual (n=49) and vacuum (n=51) groups were similar. Rate of all-cause complications was higher in the vacuum group (5 vs. 0; P=0.03): pneumothorax (n=3), surgically treated hemothorax with subsequent death (n=1) and reexpansion pulmonary edema causing respiratory failure (n=1), as was rate of early termination (8 vs. 1; P=0.018). The vacuum group exhibited greater pain during drainage (P<0.05), shorter drainage time (P<0.01), no association with volume removed (P>0.05), and lower inverse rate of removal (P≤0.01)., Conclusion: Despite requiring less time, vacuum aspiration during thoracentesis was associated with higher rates of complication and of early termination of the procedure and greater pain. Although larger studies are needed, this pilot study suggests that manual aspiration provides greater safety and patient comfort.

Background: Post-extubation dysphagia is associated with an increased incidence of nosocomial pneumonias, longer hospitalizations, and higher re-intubation rates. The purpose of this study was to determine if it is necessary to delay swallow evaluation for 24 hours post-extubation., Methods: A prospective investigation of swallowing was conducted at 1, 4, and 24 hours post-extubation to determine if it is necessary to delay swallow evaluation following intubation. Participants were 202 adults from 5 different intensive care units (ICU)., Results: A total of 166 of 202 (82.2%) passed the Yale Swallow Protocol at 1 hour post-extubation, with an additional 11 (177/202; 87.6%) at 4 hours, and 8 more (185/202; 91.6%) at 24 hours. Only intubation duration ≥4 days was significantly associated with nonfunctional swallowing., Conclusions: We found it is not necessary to delay assessment of swallowing in individuals who are post-extubation. Specifically, the majority of patients in our study (82.2%) passed a swallow screening at 1 hour post-extubation.

1) To show how to exploit the information contained in the trajectories of time-varying patient clinical data for dynamic predictions of mortality in the ICU; and 2) to demonstrate the additional predictive value that can be achieved by incorporating this trajectory information., Design: Observational, retrospective study of patient medical records for training and testing of statistical learning models using different sets of predictor variables., Setting: Medical ICU at the Yale-New Haven Hospital., Subjects: Electronic health records of 3,763 patients admitted to the medical ICU between January 2013 and January 2015., Interventions: None., Measurements and Main Results: Six-hour mortality predictions for ICU patients were generated and updated every 6 hours by applying the random forest classifier to patient time series data from the prior 24 hours. The time series were processed in different ways to create two main models: 1) manual extraction of the summary statistics used in the literature (min/max/median/first/last/number of measurements) and 2) automated extraction of trajectory features using machine learning. Out-of-sample area under the receiver operating characteristics curve and area under the precision-recall curve ("precision" refers to positive predictive value and "recall" to sensitivity) were used to evaluate the predictive performance of the two models. For 6-hour prediction and updating, the second model achieved area under the receiver operating characteristics curve and area under the precision-recall curve of 0.905 (95% CI, 0.900-0.910) and 0.381 (95% CI, 0.368-0.394), respectively, which are statistically significantly higher than those achieved by the first model, with area under the receiver operating characteristics curve and area under the precision-recall curve of 0.896 (95% CI, 0.892-0.900) and 0.905 (95% CI, 0.353-0.379). The superiority of the second model held true for 12-hour prediction/updating as well as for 24-hour prediction/updating., Conclusions: We show that statistical learning techniques can be used to automatically extract all relevant shape features for use in predictive modeling. The approach requires no additional data and can potentially be used to improve any risk model that uses some form of trajectory information. In this single-center study, the shapes of the clinical data trajectories convey information about ICU mortality risk beyond what is already captured by the summary statistics currently used in the literature., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright (c) 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: To address the competing risk of death in longitudinal studies of older persons, we demonstrate sensitivity analyses that evaluate robustness of associations between exposures and three outcome types: dichotomous, count, and time to event., Design: A secondary analysis of data from a prospective cohort study., Setting: Community-based data from the Precipitating Events Project in New Haven, CT., Participants: Persons 70 years and older who were initially community dwelling and without disability in the four basic activities of daily living (N = 754)., Measurements: Missing outcome values from decedents were multiply imputed under different scenarios. Three outcomes were examined: dichotomous fall-related hospitalization (FRH); a count (0-13) of total disability in each of the 6 months after discharge; and days to functional recovery among those whose disability worsened in the hospital. Each outcome had a different exposure: for dichotomous, indicators of being overweight or obese; for count, frailty from the Fried phenotype (0-5, where not frail = 0, prefrail = 1-2, and frail = 3-5); for days to recovery, vision impairment., Results: For FRH, being overweight or obese lost significance when decedents were kept in the risk pool without outcome events for over 10 years. For disability count and time to recovery, with follow-up of 6 months, exposures only lost significance under highly implausible clinical scenarios., Conclusion: This method facilitates evaluation of potential bias from the competing risk of death in longitudinal studies for nondeath outcomes that are not necessarily time to event. Results suggest that death introduces substantive bias when long-term follow-up results in cumulatively high levels of mortality. J Am Geriatr Soc 67:357-362, 2019., (© 2018 The American Geriatrics Society.)

Background: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU)., Methods: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation., Results: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms., Conclusions: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).

Purpose: Critically ill patients experience significant sleep disruption. In this study of ICU patients with delirium, we evaluated associations between the loss of stage N2 features (K-complexes, sleep spindles), grade of encephalopathy based on electroencephalography (EEG), and intensive care unit (ICU) outcomes. We hypothesized that loss of stage N2 features is associated with more severe grades of encephalopathy and worse ICU outcomes including death., Materials and Methods: This was an observational cohort study of 93 medical ICU patients without primary acute brain injury who underwent continuous EEG. Type and severity of critical illness, sedative-hypnotic use, length of stay, modified Rankin Scale at hospital discharge, and death during hospitalization were abstracted from the medical record. EEG was evaluated for grade of encephalopathy and sleep features., Results: Patients without K-complexes or without sleep spindles had more severe encephalopathy and higher odds of death. The odds ratio for patients without K-complexes was 18.8 (p = .046). The odds ratio for patients without sleep spindles was 6.3 (p = .036)., Conclusions: Loss of stage N2 features is common and associated with more severe encephalopathy and higher odds of death. The absence of either Stage N2 feature, K complexes or sleep spindles, may have important prognostic value., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Intensive care unit (ICU) sleep disturbance is severe and potentially related to abnormal light and sound exposure., Objectives: To assess the prevalence of measures of light and sound disturbance in ICU patient rooms, and whether these could be modified by a sleep-promotion intervention., Methods: This observational study with a before and after design for a quality improvement initiative surveyed environmental factors in ICU rooms at 01:00 08:00, and 12:00. Surveys assessed light usage, television usage, window shade position, and room door/curtain position. Factors were compared before and after an ICU sleep-promotion intervention., Results: 990 (pre-intervention) and 819 (post-intervention) occupied rooms were surveyed. Pre-intervention, the prevalence of night-time factors included: bright lights on (21%), television on (46%), and room door open (94%). Post-intervention, more rooms had all lights off at night (41% v 50%, p = 0.04), and fewer rooms had open door curtains (57% v 42%, p = 0.001) and window shades (78% v 62%, p = 0.002)., Conclusions: Disruptive environmental factors are common in the ICU. Some factors improve with sleep-promotion interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU., Design: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017., Methods: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified., Results: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation., Conclusions: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Introduction: Patients in the intensive care unit (ICU) have significantly disrupted sleep. Sleep disruption is believed to contribute to ICU delirium, and ICU delirium is associated with increased mortality. Experts recommend sleep promotion as a means of preventing or shortening the duration of delirium. ICU Sleep promotion protocols are highly complex and difficult to implement. Our objective is to describe the development, pilot implementation, and revision of a medical ICU sleep promotion protocol., Methods: Naptime is a clustered-care intervention that provides a rest period between 00:00 and 04:00. We used literature review, medical chart review, and stakeholder interviews to identify sources of overnight patient disturbance. With stakeholder input, we developed an initial protocol that we piloted on a small scale. Then, using protocol monitoring and stakeholder feedback, we revised Naptime and adapted it for unitwide implementation., Results: We identified sound, patient care, and patient anxiety as important sources of overnight disturbance. The pilot protocol altered the timing of routine care with a focus on medications and laboratory draws. During the pilot, there were frequent protocol violations for laboratory draws and for urgent care. Stakeholder feedback supported revision of the protocol with a focus on providing 60- to 120-minute rest periods interrupted by brief clusters of care between 00:00 and 04:00., Discussion: Four-hour blocks of rest may not be possible for all medical ICU patients, but interruptions can be minimized to a significant degree. Involvement of all stakeholders and frequent protocol reevaluation are needed for successful adoption of an overnight rest period., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.