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Visual working memory is thought to have a fixed capacity limit. However, recent evidence suggests that a greater number of real-world objects than simple features (i.e., colors) can be maintained, an effect termed the object benefit. Here, we examined whether this object benefit in visual working memory is due to qualitatively different memory processes employed for meaningful stimuli compared to simple features. In online samples of young adults, real-world objects were better remembered than colors, had higher measures of recollection, and showed a greater proportion of high-confidence responses (Exp. 1). Objects were also remembered better than their scrambled counterparts (Exp. 2), suggesting that this benefit is related to semantic information, rather than visual complexity. Critically, the specific objects that were likely to be remembered with high confidence were highly correlated across experiments, consistent with the idea that some objects are more memorable than others. Visual working memory performance for the least-memorable objects was worse than that of colors and scrambled objects. These findings suggest that real-world objects give rise to recollective, or at least high-confidence, responses at retrieval that may depend on activation of semantic features, but that this effect is limited to certain objects., (© 2024. The Psychonomic Society, Inc.)

Objectives: Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium., Design: Prospective cohort study., Setting: A 32-bed academic medical-surgical ICU., Patients: Critically ill adults ( n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment., Interventions: None., Measurements and Main Results: Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0-10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1-3/CPOT = 1-2), moderate (NRS = 4-6/CPOT = 3-4), or severe (NRS = 7-10/CPOT = 5-8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated., Results: Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days ( p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76-1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose., Conclusions: After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required., Competing Interests: Dr. Devlin disclosed he has received unrelated grant support from the National Institute of Aging, Agency for Healthcare Research and Quality, Sedana Medical, and BioXcel Therapeutics and has served as a consultant to BioExcel Therapeutics, Ceribell, and La Jolla Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Existing models to predict fall-related injuries (FRI) in nursing homes (NH) focus on hip fractures, yet hip fractures comprise less than half of all FRIs. We developed and validated a series of models to predict the absolute risk of FRIs in NH residents., Methods: Retrospective cohort study of long-stay US NH residents (≥100 days in the same facility) between January 1, 2016 and December 31, 2017 (n = 733,427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through LASSO logistic regression in a 2/3 random derivation sample and tested in a 1/3 validation sample. Sub-distribution hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated for 6-month and 2-year follow-up. Discrimination was evaluated via C-statistic, and calibration compared the predicted rate of FRI to the observed rate. To develop a parsimonious clinical tool, we calculated a score using the five strongest predictors in the Fine-Gray model. Model performance was repeated in the validation sample., Results: Mean (Q1, Q3) age was 85.0 (77.5, 90.6) years and 69.6% were women. Within 2 years of follow-up, 43,976 (6.0%) residents experienced ≥1 FRI. Seventy predictors were included in the model. The discrimination of the 2-year prediction model was good (C-index = 0.70), and the calibration was excellent. Calibration and discrimination of the 6-month model were similar (C-index = 0.71). In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14-2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94-2.12). Performance results were similar in the validation sample., Conclusions: We developed and validated a series of risk prediction models that can identify NH residents at greatest risk for FRI. In NH, these models should help target preventive strategies., (© 2023 The American Geriatrics Society.)

Objective: To examine prevalence of Alzheimer Disease and related dementias (ADRD) and patient characteristics as a function of comorbid insomnia and/or depression among heart failure (HF) patients discharged from hospitals., Design: Retrospective cohort descriptive epidemiology study., Setting: VA Hospitals., Participants: N = 373,897 Veterans hospitalized with heart failure from October 1, 2011 until September 30, 2020., Measurements: We examined VA and Center for Medicare & Medicaid Services (CMS) coding in the year prior to admission using published ICD-9/10 codes for dementia, insomnia, and depression. The primary outcome was the prevalence of ADRD and the secondary outcomes were 30-day and 365-day mortality., Results: The cohort were predominantly older adults (mean age = 72 years, SD = 11), male (97%), and White (73%). Dementia prevalence in participants without insomnia or depression was 12%. In those with both insomnia and depression, dementia prevalence was 34%. For insomnia alone and depression alone, dementia prevalence was 21% and 24%, respectively. Mortality followed a similar pattern with highest 30-day and 365-day mortality higher in those with both insomnia and depression., Conclusions: These results suggest that persons with both insomnia and depression are at an increased risk of ADRD and mortality compared to persons with one or neither condition. Screening for both insomnia and depression, especially in patients with other ADRD risk factors, could lead to earlier identification of ADRD. Understanding comorbid conditions which may represent earlier signs of ADRD may be critical in the identification of ADRD risk., Competing Interests: DISCLOSURES The authors have no disclosures to report., (Copyright © 2023 American Association for Geriatric Psychiatry. All rights reserved.)

Claims data are a valuable resource for studying Alzheimer's disease and related dementias (ADRD). Alzheimer's disease and related dementias is often identified using a list of claims codes and a fixed lookback period of 3 years of data. However, a 1-year lookback or an approach using all-available lookback data could be beneficial based on different research questions. Thus, the purpose of this study was to compare 1-year and all-available lookback approaches to ascertaining ADRD compared to the standard 3-year approach. Using a cohort of Veterans hospitalized for heart failure (N = 373, 897), our results suggested high agreement (93% or greater) between the lookback periods. The 1-year lookback period had lower sensitivity (60%) and underestimated the prevalence of ADRD. These results suggest that 1-year and all-available lookback periods are viable approaches when using claims data.

To encourage person-centered care, the Centers for Medicare and Medicaid require nursing homes to measure resident preferences using the Preferences Assessment Tool (PAT). No known research has examined the implications of respondent type (i.e., resident, proxy, staff) on preference importance; therefore, the purpose of this study was to compare the importance of preferences depending on which respondent completed the PAT. Participants included 16,111 Veterans discharged to community-based skilled nursing facilities after hospitalization for heart failure. A majority (95%) of residents completed the PAT compared to proxy (3%) and staff (2%). Proxy responders were both more and less likely to indicate individual preferences as important compared to residents. Staff members were consistently less likely to indicate all preferences as important compared to residents. Findings from this study emphasize the need for proxy and staff to find methods to better understand residents' preferences when residents are not able to participate in assessments.

Background: Fall-related injuries (FRIs) are a leading cause of morbidity, mortality, and costs among nursing home (NH) residents. Carefully defining FRIs in administrative data is essential for improving injury-reduction efforts. We developed a series of novel claims-based algorithms for identifying FRIs in long-stay NH residents., Methods: This is a retrospective cohort of residents of NH residing there for at least 100 days who were continuously enrolled in Medicare Parts A and B in 2016. FRIs were identified using 4 claims-based case-qualifying (CQ) definitions (Inpatient [CQ1], Outpatient and Provider with Procedure [CQ2], Outpatient and Provider with Fall [CQ3], or Inpatient or Outpatient and Provider with Fall [CQ4]). Correlation was calculated using phi correlation coefficients., Results: Of 153 220 residents (mean [SD] age 81.2 [12.1], 68.0% female), we identified 10 104 with at least one FRI according to one or more CQ definition. Among 2 950 residents with hip fractures, 1 852 (62.8%) were identified by all algorithms. Algorithm CQ4 (n = 326-2 775) identified more FRIs across all injuries while CQ1 identified less (n = 21-2 320). CQ2 identified more intracranial bleeds (1 028 vs 448) than CQ1. For nonfracture categories, few FRIs were identified using CQ1 (n = 20-488). Of the 2 320 residents with hip fractures identified by CQ1, 2 145 (92.5%) had external cause of injury codes. All algorithms were strongly correlated, with phi coefficients ranging from 0.82 to 0.99., Conclusions: Claims-based algorithms applied to outpatient and provider claims identify more nonfracture FRIs. When identifying risk factors, stakeholders should select the algorithm(s) suitable for the FRI and study purpose., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery., Methods: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month., Results: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed., Conclusions: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Purpose: To study the incidence, predictors, and outcomes of diarrhea during the stay in the intensive care unit (ICU)., Methods: Prospective cohort of consecutive adults in the ICU for > 24 h during a 10-week period across 12 intensive care units (ICUs) internationally. The explored outcomes were: (1) incidence of diarrhea, (2) Clostridioides difficile-associated diarrhea (CDAD); (3) ICU and hospital length of stay (LOS) and mortality in patients with diarrhea. We fit generalized linear models to evaluate the predictors, management, morbidity and mortality associated with diarrhea., Results: Among 1109 patients aged 61.4 (17.5) [mean (standard deviation)] years, 981(88.5%) were medical and 645 (58.2%) were mechanically ventilated. The incidence was 73.8% (818 patients, 73.8%, 95% confidence interval [CI] 71.1-76.6) using the definition of the World Health Organisation (WHO). Incidence varied across definitions (Bristol 53.5%, 95% CI 50.4-56.7; Bliss 37.7%, 95% CI 34.9-40.4). Of 99 patients with diarrhea undergoing CDAD testing, 23 tested positive (2.2% incidence, 95% CI 1.5-3.4). Independent predictors included enteral nutrition (RR 1.23, 95% CI 1.16-1.31, p < 0.001), antibiotic days (RR 1.02, 95% CI 1.02-1.03, p < 0.001), and suppositories (RR 1.14 95% CI 1.06-1.22, p < 0.001). Opiates decreased diarrhea risk (RR 0.76, 95% CI 0.68-0.86, p < 0.001). Diarrhea prompted management modifications (altered enteral nutrition or medications: RR 10.25, 95% CI 5.14-20.45, p < 0.001) or other consequences (fecal management device or CDAD testing: RR 6.16, 95% CI 3.4-11.17, p < 0.001). Diarrhea was associated with a longer time to discharge for ICU or hospital stay, but was not associated with hospital mortality., Conclusion: Diarrhea is common, has several predictors, and prompts changes in patient care, is associated with longer time to discharge but not mortality., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients . In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days., Results: Only 318 (20.6%) of the 1542 screened adults during the 1/17-10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N ( n  = 6) and P ( n  = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P  = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P  = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P  < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P  = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P  = 1.0). No patient experienced opioid withdrawal., Conclusions: Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Matthew S. Duprey et al.)

Aims: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents., Materials and Methods: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models., Results: The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise., Conclusions: Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates., (© 2021 John Wiley & Sons Ltd.)

We compared ICU nonopioid analgesic use, opioid use, and pain before and after Pain, Agitation/Sedation, Delirium, Immobility, and Sleep guideline publication at one academic center among critically ill adults receiving an opioid infusion and greater than or equal to 24 hours of mechanical ventilation after major surgery. The 2017 ( n = 77) and 2019 ( n = 57) groups were similar at baseline. The 2019 (vs 2017) patients were more likely to receive scheduled IV/oral acetaminophen (84% vs 69%; p = 0.05), less likely to receive a lidocaine patch (33% vs 50%; p = 0.05), and just as likely to receive ketamine (4% vs 3%; p = 1.0), an nonsteroidal anti-inflammatory drug (7% vs 3%; p = 0.26), or gabapentin/pregabalin (16% vs 9%; p = 0.23). Daily average opioid exposure (in IV morphine milligram equivalent) was not different (70 [42-99] [2017] vs 78 mg [49-109 mg]; p = 0.94). The 2019 (vs 2017) group spent more ICU days with severe pain ( p = 0.04). At our center, Pain, Agitation/Sedation, Delirium, Immobility, and Sleep guideline publication had little effect on nonopioid analgesic or opioid prescribing practices in critically ill surgical adults., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Studies comparing dipeptidyl peptidase-4 inhibitors (DPP4Is) to sulfonylureas (SUs) are unavailable for frail older adults, especially nursing home (NH) residents. We examined the effects of DPP4Is versus SUs on severe adverse glycemic events, cardiovascular events, and death among NH residents., Methods: We conducted a national retrospective cohort study of long-stay NH residents aged ≥65 years using 2008-2010 national US Minimum Data Set clinical assessment data and linked Medicare claims. Exposure was new DPP4I versus new SU use assessed via Medicare Part D drug claims. One-year outcomes were severe hypoglycemia, severe hyperglycemia, acute myocardial infarction (AMI), heart failure (HF), major adverse cardiovascular events plus HF (MACE+HF), and death. We compared outcomes after propensity score matching using Cox proportional hazards regression models., Results: The cohort (N = 2016) had a mean (SD) age of 81 (8.1) years and was 72% female. Compared with SU users, DPP4I users had a lower 1-year rate of severe hypoglycemic events (HR = 0.57, 95% CI 0.34-0.94), but statistically similar rates of severe hyperglycemic events (HR = 0.94, 95% CI 0.52-1.72), AMI (HR = 0.76, 95% CI 0.44-1.30), HF (HR = 1.01, 95% CI 0.79-1.30), MACE+HF (HR = 0.90, 95% CI 0.72-1.12), and death (HR = 0.97, 95% CI 0.86-1.10)., Conclusions: DPP4Is should be a preferred treatment option over SUs for NH residents and other frail older adults given the importance of avoiding hypoglycemia., (© 2021 The American Geriatrics Society.)

Rationale: It is unclear whether opioid use increases the risk of ICU delirium. Prior studies have not accounted for confounding, including daily severity of illness, pain, and competing events that may preclude delirium detection. Objectives: To evaluate the association between ICU opioid exposure, opioid dose, and delirium occurrence. Methods: In consecutive adults admitted for more than 24 hours to the ICU, daily mental status was classified as awake without delirium, delirium, or unarousable. A first-order Markov model with multinomial logistic regression analysis considered four possible next-day outcomes (i.e., awake without delirium, delirium, unarousable, and ICU discharge or death) and 11 delirium-related covariables (baseline: admission type, age, sex, Acute Physiology and Chronic Health Evaluation IV score, and Charlson comorbidity score; daily: ICU day, modified Sequential Organ Failure Assessment, ventilation use, benzodiazepine use, and severe pain). This model was used to quantify the association between opioid use, opioid dose, and delirium occurrence the next day. Measurements and Main Results: The 4,075 adults had 26,250 ICU days; an opioid was administered on 57.0% ( n  = 14,975), severe pain occurred on 7.0% ( n  = 1,829), and delirium occurred on 23.5% ( n  = 6,176). Severe pain was inversely associated with a transition to delirium (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.53-0.97). Any opioid administration in awake patients without delirium was associated with an increased risk for delirium the next day [OR, 1.45; 95% CI, 1.24-1.69]. Each daily 10-mg intravenous morphine-equivalent dose was associated with a 2.4% increased risk for delirium the next day. Conclusions: The receipt of an opioid in the ICU increases the odds of transitioning to delirium in a dose-dependent fashion.

Objectives: Haloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality., Design: Post hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial., Setting: Fourteen Dutch ICUs between July 2013 and December 2016., Patients: One-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days., Interventions: Patients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion., Measurements and Main Results: Patients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2-7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0-3.8 mg] daily) for 6 days (3-11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91-0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96-0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence., Conclusions: Treatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results., Competing Interests: Dr. Duprey’s efforts are supported by the National Institute of Aging 1F31AG066460-01. Drs. Duprey, Devlin, Briesacher, and Saczynski received support for article research from the National Institutes of Health. Dr. Duprey disclosed off-label product use of haloperidol for delirium. Dr. van den Boogaard’s institution received funding and support for article research from ZonMw. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown., Methods: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months., Results: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups., Conclusions: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.)., (Copyright © 2021 Massachusetts Medical Society.)

We retrospectively characterized scheduled, newly initiated, nocturnal neuroactive medication use, and related clinician documentation, in a cohort of consecutive adults admitted greater than or equal to 24 hours to seven different medical/surgical ICUs at two academic centers who had not received a scheduled nocturnal neuroactive medication prior to admission, over a 5-month period (April 1, 2017, to August 31, 2017). A total of 207 different newly initiated, scheduled nocturnal neuroactive medication orders were written (melatonin agonist 101 [48.8%], antipsychotic 80 [38.6%], antidepressant 17 [8.2%], benzodiazepine 9 [4.3%]) in 189 (9.7%) of the 1,955 patients. Among the 1,553 nights, the 189 patients spent in the ICU, a scheduled nocturnal neuroactive medication was administered on 1,103 (71%), an "as needed" nocturnal neuroactive medication was solely administered on 183 (11.8%), delirium occurred on 736 (47.4%), and nurses were twice as likely as physicians (28.8% vs 11.4%; p < 0.0001) to document a note about sleep quality. Among the 69.8% of patients discharged to the floor, and the 64.5% from the hospital, the scheduled nocturnal neuroactive medication was continued in 85.6% and 87.3%, respectively. Scheduled nocturnal neuroactive medication initiation is common, often continued beyond hospital discharge, and poorly documented., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Methods for pharmacoepidemiologic studies of large-scale data repositories are established. Although clinical cohorts of older adults often contain critical information to advance our understanding of medication risk and benefit, the methods best suited to manage medication data in these samples are sometimes unclear and their degree of validation unknown. We sought to provide researchers, in the context of a clinical cohort study of delirium in older adults, with guidance on the methodological tools to use data from clinical cohorts to better understand medication risk factors and outcomes., Design: Prospective cohort study., Setting: The Successful Aging After Elective Surgery (SAGES) prospective cohort., Participants: A total of 560 older adults (aged ≥70 years) without dementia undergoing elective major surgery., Measurements: Using the SAGES clinical cohort, methods used to characterize medications were identified, reviewed, analyzed, and distinguished by appropriateness and degree of validation for characterizing pharmacoepidemiologic data in smaller clinical data sets., Results: Medication coding is essential; the American Hospital Formulary System, most often used in the United States, is not preferred over others. Use of equivalent dosing scales (e.g., morphine equivalents) for a single medication class (e.g., opioids) is preferred over multiclass analgesic equivalency scales. Medication aggregation from the same class (e.g., benzodiazepines) is well established; the optimal prevalence breakout for aggregation remains unclear. Validated scale(s) to combine structurally dissimilar medications (e.g., anticholinergics) should be used with caution; a lack of consensus exists regarding the optimal scale. Directed acyclic graph(s) are an accepted method to conceptualize causative frameworks when identifying potential confounders. Modeling-based strategies should be used with evidence-based, a priori variable-selection strategies., Conclusion: As highlighted in the SAGES cohort, the methods used to classify and analyze medication data in clinically rich cohort studies vary in the rigor by which they have been developed and validated., (© 2020 The American Geriatrics Society.)

Since 2014, the Society of Critical Care Medicine has encouraged "live-tweeting" through the use of specific hashtags at each annual Critical Care Congress. We describe how the digital footprint of the Society of Critical Care Medicine Congress on Twitter has evolved at a time when social media use at conferences is becoming increasingly popular., Design: We used Symplur Signals (Symplur LLC, Pasadena, CA) to track all tweets containing the Society of Critical Care Medicine Congress hashtag for each annual meeting between 2014 and 2020. We collected data on the number of tweets, tweet characteristics, and impressions (i.e., potential views) for each year and data on the characteristics of the top 100 most actively tweeting users of that Congress., Setting: Twitter., Subjects: Users tweeting with the Critical Care Congress hashtag., Interventions: Not applicable., Measurements and Main Results: The Critical Care Congress digital footprint grew substantially from 2014 to 2020. The 2014 Critical Care Congress included 1,629 tweets by 266 users, compared with 29,657 tweets by 3,551 participants in 2020; average hourly tweets increased from 9.7 to 177. The percentage of tweets with mentions of other users and tweets with visual media increased. Users attending the conference were significantly more likely to compose original tweets, whereas those tweeting from afar were more likely to retweet Critical Care Congress content. There was a yearly increase in content-specific hashtags used in conjunction with Critical Care Congress hashtags ( n = 429 in 2014 to n = 22,272 in 2020), most commonly related to pediatrics (18% of all hashtags), mobility/rehab (9%), sepsis (7%) social media (6%), and ICU burnout (1%)., Conclusions: There has been significant growth in live-tweeting at the Critical Care Congress, along with the increased use of content-specific hashtags and visual media. This digital footprint is largely driven by a proportion of highly engaged users. As medical conferences transition to completely or partially online platforms, understanding of the digital footprint is crucial for success., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Whether and how delirium and sleep quality in the intensive care unit (ICU) are linked remains unclear. A recent randomised trial reported nocturnal low-dose dexmedetomidine (DEX) significantly reduces incident ICU delirium. Leeds Sleep Evaluation Questionnaire (LSEQ) scores were similar between intervention (DEX; n=50) and control (placebo (PLA); n=50) groups. We measured the association between morning LSEQ and delirium occurrence in the prior 24 hours (retrospective analysis) and the association between morning LSEQ and delirium occurrence in the following 24 hours (predictive analysis)., Design: Post hoc analysis of randomised controlled trial data., Participants: Adult ICU patients (n=100) underwent delirium screening twice a day using the Intensive Care Delirium Screening Checklist (ICDSC) if Richmond Agitation Sedation Scale (RASS) was ≥-3 and patient-reported sleep quality evaluations at 09:00 daily with the LSEQ if RASS was ≥-1., Outcomes: The analysis included all 24-hour study periods with LSEQ documentation and matched delirium screening in coma-free patients. Separate logistic regression models controlling for age, baseline Acute Physiology and Chronic Health Evaluation II score and DEX/PLA allocation evaluated the association between morning LSEQ and delirium occurrence for both retrospective and predictive analyses., Results: The 100 patients spent 1115 24-hour periods in the ICU. Coma, delirium and no delirium occurred in 130 (11.7%), 114 (10.2%) and 871 (78.1%), respectively. In the retrospective analysis, when an LSEQ result was preceded by an ICDSC result (439/985 (44.6%) 24-hour periods), delirium occurred during 41/439 (9.3%) periods. On regression analysis, the LSEQ score had no relationship to prior delirium occurrence (OR (per every 1 point average LSEQ change) 0.97, 95% CI 0.72 to 1.31). For the predictive analysis, among the 387/985 (39.1%) 24-hour periods where an LSEQ result was followed by an ICDSC result, delirium occurred during 56/387 (14.5%) periods. On regression analysis, the LSEQ score did not predict subsequent delirium occurrence (OR (per 1 point LSEQ change) 1.02, 95% CI 0.99 to 1.05)., Conclusions: The sleep quality ICU patients perceive neither affects nor predicts delirium occurrence., Trial Registration Number: NCT01791296., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: While delirium prevalence and duration are each associated with increased 30-day, 6-month, and 1-year mortality, the association between incident ICU delirium and mortality remains unclear. We evaluated the association between both incident ICU delirium and days spent with delirium in the 28 days after ICU admission and mortality within 28 and 90 days., Methods: Secondary cohort analysis of a randomized, double-blind, placebo-controlled trial conducted among 1495 delirium-free, critically ill adults in 14 Dutch ICUs with an expected ICU stay ≥2 days where all delirium assessments were completed. In the 28 days after ICU admission, patients were evaluated for delirium and coma 3x daily; each day was coded as a delirium day [≥1 positive Confusion Assessment Method for the ICU (CAM-ICU)], a coma day [no delirium and ≥ 1 Richmond Agitation Sedation Scale (RASS) score ≤ - 4], or neither. Four Cox-regression models were constructed for 28-day mortality and 90-day mortality; each accounted for potential confounders (i.e., age, APACHE-II score, sepsis, use of mechanical ventilation, ICU length of stay, and haloperidol dose) and: 1) delirium occurrence, 2) days spent with delirium, 3) days spent in coma, and 4) days spent with delirium and/or coma., Results: Among the 1495 patients, 28 day mortality was 17% and 90 day mortality was 21%. Neither incident delirium (28 day mortality hazard ratio [HR] = 1.02, 95%CI = 0.75-1.39; 90 day mortality HR = 1.05, 95%CI = 0.79-1.38) nor days spent with delirium (28 day mortality HR = 1.00, 95%CI = 0.95-1.05; 90 day mortality HR = 1.02, 95%CI = 0.98-1.07) were significantly associated with mortality. However, both days spent with coma (28 day mortality HR = 1.05, 95%CI = 1.02-1.08; 90 day mortality HR = 1.05, 95%CI = 1.02-1.08) and days spent with delirium or coma (28 day mortality HR = 1.03, 95%CI = 1.00-1.05; 90 day mortality HR = 1.03, 95%CI = 1.01-1.06) were significantly associated with mortality., Conclusions: This analysis suggests neither incident delirium nor days spent with delirium are associated with short-term mortality after ICU admission., Trial Registration: ClinicalTrials.gov, Identifier NCT01785290 Registered 7 February 2013.

Background: Serious cardiovascular adverse events (SCAEs) associated with intravenous sedatives remain poorly characterized., Objective: The objective of this study was to compare SCAE incidence, types, and mortality between intravenous benzodiazepines (i.e., diazepam, lorazepam, and midazolam), dexmedetomidine, and propofol in the USA over 8 years regardless of the clinical setting where it was administered., Methods: The Food and Drug Administration's MedWatch Adverse Event Reporting System was searched between 2004 and 2011 using the Evidex ® platform from Advera Health Analytics, Inc. to identify all reports that included one or more of ten different SCAEs (package insert incidence ≥ 1%) and where an intravenous benzodiazepine, dexmedetomidine, or propofol was the primary suspected drug., Results: Among the 2326 Food and Drug Administration's MedWatch Adverse Event Reporting System cases reported, 394 (16.9%) were related to a SCAE. The presence of a SCAE (vs. a non-SCAE) is associated with higher mortality (34 vs. 8%, p < 0.001). The percentage of cases with one or more SCAE, the case mortality rate (%), and the incidence of each SCAE (per 10 6 days of sedative exposure), respectively, were benzodiazepines (14, 26, 13) [diazepam (13, 23, 31); lorazepam (15, 43, 14); midazolam (14, 20, 11)]; dexmedetomidine (40, 15, 13); and propofol (17, 39, 7). Propofol (vs. either a benzodiazepine or dexmedetomidine) was associated with more total SCAEs (268 vs. 126, p < 0.001) but a lower incidence (per 10 6 days of sedative exposure) of SCAE (7 vs. 13, p = 0.0001) and cardiac arrest [6.3 (benzodiazepine) vs. 6.7 (dexmedetomidine) vs. 1.4 (propofol), p < 0.0001]., Conclusions: Serious cardiac adverse events account for nearly one-fifth of intravenous sedative Food and Drug Administration's MedWatch Adverse Event Reporting System reports. These SCAEs appear to be associated with greater mortality than non-cardiac serious adverse events. Serious cardiac events may be more prevalent with either benzodiazepines or dexmedetomidine than propofol.

Objectives: To identify the incidence, characteristics, and predictors for 30 and 90-day readmission among acutely hospitalized patients with opioid use disorder (OUD)., Methods: This retrospective, cohort study evaluated consecutive adults with OUD admitted to an academic medical center over a 5-year period (10/1/11 to 9/30/16). Multivariable logistic regression was used to determine independent predictors for 30 and 90-day readmissions based on pertinent admission, hospital, and discharge variables collected via chart review and found to be different (with a P < 0.10) on univariate analysis., Results: Among the 470 adults (mean age 43.1 ± 12.8 years, past heroin use 77.9%; admission opioid agonist therapy use [buprenorphine 22.6%; methadone 27.0%]; medical [vs surgical] admission 75.3%, floor [vs ICU] admission 93.0%, in-hospital mortality 0.9%), 85 (18.2%) and 151 (32.1%) were readmitted within 30 and 90 days, respectively. Among the 90-day readmitted patients, median time to first readmission was 26 days. Buprenorphine use (vs no use) at index hospital admission was independently associated with reduced 30-day (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.24-0.93) and 90-day (OR 0.57, 95% CI 0.34-0.96) readmission; prior heroin (vs prescription opioid) use was associated with reduced 90-day readmission (OR 0.59, 95% CI 0.37-0.94) and length of hospital stay was associated with both greater 30-day (OR 1.02, 95% CI 1.01-1.05) and 90-day (OR 1.04, 95% CI 1.01-1.06) readmission rates., Conclusions: Among patients with OUD taking buprenorphine at the time of hospital admission, 30-day and 90-day hospital readmission was reduced by 53% and 43%, respectively.

Hospitals often perform urine drug screens (UDS) upon inpatient admission to confirm self-reported psychoactive substance use for patients with opioid use disorder (OUD). We sought to evaluate the agreement between UDS and patient self-report for psychoactive substances detected with UDS for adults with OUD admitted to hospital. For 11 substance categories, we evaluated agreement between the UDS and the documented history over a 5-year period for consecutive adults admitted to one academic center with a history of OUD. Among the 153 patients, overall agreement across the 1683 different history/UDS pairs (i.e. either history+/UDS + or history-/UDS-) was high (81.3%) but varied (from lowest to highest) by substance [opiates (56.9%), benzodiazepines (66.0%), 6-acetylmorphine (67.3%), cocaine (81.0%), cannabinoids (81.0%), methadone (83.7%), buprenorphine (85.0%), amphetamine (94.8%), barbiturates (95.4%), and phencyclidine (98.7%)]. History+/UDS- pair mismatches were most frequent for 6-acetylmorphine (32.7%), methadone (14.3%) and oxycodone (12.4%); history-/UDS + pair mismatches were most frequent for opiates (43.1%), benzodiazepines (24.8%) and cannabinoids (18.3%). The change in agreement over time of self-reported heroin use may reflect an increasing number of patients unknowingly using illicit fentanyl products. Among hospitalized patients with OUD, agreement between reported psychoactive substance use history and UDS results is strong with the exception of opiates, heroin, and benzodiazepines., Competing Interests: Disclosure statement The authors declare that they have no conflict of interest

Rationale: Dexmedetomidine is associated with less delirium than benzodiazepines and better sleep architecture than either benzodiazepines or propofol; its effect on delirium and sleep when administered at night to patients requiring sedation remains unclear., Objectives: To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill adults., Methods: This two-center, double-blind, placebo-controlled trial randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (9:30 p.m. to 6:15 a.m.) intravenous dexmedetomidine (0.2 μg/kg/h, titrated by 0.1 μg /kg/h every 15 min until a goal Richmond Agitation and Sedation Scale score of -1 or maximum rate of 0.7 μg/kg/h was reached) or placebo until ICU discharge. During study infusions, all sedatives were halved; opioids were unchanged. Delirium was assessed using the Intensive Care Delirium Screening Checklist every 12 hours throughout the ICU admission. Sleep was evaluated each morning by the Leeds Sleep Evaluation Questionnaire., Measurements and Main Results: Nocturnal dexmedetomidine (vs. placebo) was associated with a greater proportion of patients who remained delirium-free during the ICU stay (dexmedetomidine [40 (80%) of 50 patients] vs. placebo [27 (54%) of 50 patients]; relative risk, 0.44; 95% confidence interval, 0.23-0.82; P = 0.006). The average Leeds Sleep Evaluation Questionnaire score was similar (mean difference, 0.02; 95% confidence interval, 0.42-1.92) between the 34 dexmedetomidine (average seven assessments per patient) and 30 placebo (six per patient) group patients able to provide one or more assessments. Incidence of hypotension, bradycardia, or both did not differ significantly between groups., Conclusions: Nocturnal administration of low-dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay; patient-reported sleep quality appears unchanged. Clinical trial registered with www.clinicaltrials.gov (NCT01791296).