Risk factors for dementia in older intensive care unit (ICU) survivors.

INTRODUCTION: As the number of older intensive care unit (ICU) survivors grows, there is an urgent need to identify modifiable risk factors for post-ICU dementia. METHODS: We performed a secondary data analysis of 3144 ICU patients ≥ 50 years of age without a history of dementia or severe mental illness who were screened as part of the Pharmacological Management of Delirium (PMD) study. Delirium was assessed using the Confusion Assessment Method for the ICU. Dementia was identified using International Classification of Diseases Ninth and Tenth revision codes for dementia or prescription of anti-dementia medication. RESULTS: Average age (standard deviation) was 65.2 ± 9.5 years; 50.4% were female; and 37.3% were Black. Analyses identified stroke (adjusted hazard ratio [HR] 2.49; 95% confidence interval [CI: 1.52, 4.07], P < 0.001), and depression (adjusted HR 3.03; 95% CI [1.80, 5.10], P < 0.001) as post-ICU risk factors for dementia. DISCUSSION: Future studies will need to examine whether interventions targeting post-ICU stroke and depression can lower dementia incidence in ICU survivors. HIGHLIGHTS: Risk factors for post-intensive care unit (ICU) dementia were distinct from those of Alzheimer's disease. Cardiovascular risk factors were not associated with dementia in older ICU survivors. Post-ICU stroke was associated with a higher risk of dementia in older ICU survivors. Post-ICU depression was associated with a higher risk of dementia in older ICU survivors.

Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation.

OBJECTIVES: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. DESIGN: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. SETTING: Tertiary-care center in Indianapolis, IN, United States. PATIENTS: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). D-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if D-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if D-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). CONCLUSIONS: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. D-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.

Biomarkers of Delirium Duration and Delirium Severity in the ICU.

OBJECTIVES: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. DESIGN: Observational study. SETTING: Three Indianapolis hospitals. PATIENTS: Three-hundred twenty-one critically ill delirious patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100ß levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100ß levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100ß lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100ß levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. CONCLUSIONS: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.

Associations Between Mean Arterial Pressure and Poor ICU Outcomes in Critically Ill Patients With Cirrhosis: Is 65 The Sweet Spot?

OBJECTIVES: Mean arterial pressure is critically important in patients with cirrhosis in the ICU, however, there is limited data to guide therapies and targets. DESIGN: Retrospective observational study. SETTING: Tertiary care ICU. PATIENTS: Two hundred and seventy-three critically ill patients with cirrhosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed a comprehensive time-weighted mean arterial pressure analysis (time-weighted-average-mean arterial pressure and cumulative-time-below various mean arterial pressure-thresholds) during the first 24-hours after ICU admission (median: 25 mean arterial pressure measurements per-patient). Time-weighted-average-mean arterial pressure captures both the severity and duration of hypotension below a mean arterial pressure threshold and cumulative-time-below is the total time spent below a mean arterial pressure threshold. Individual univariable and multivariable logistic regression models were assessed for each time-weighted-average-mean arterial pressure and cumulative-time-below mean arterial pressure threshold (55, 60, 65, 70, and 75 mm Hg) for ICU-mortality. Time-weighted-average-mean arterial pressure: for 1 mm Hg decrease in mean arterial pressure below 75, 70, 65, 60, and 55 mm Hg, the odds for ICU-mortality were 14%, 18%, 26%, 41%, and 74%, respectively (p < 0.01, all thresholds). The association between time-weighted-average-mean arterial pressure and ICU-mortality for each threshold remained significant after adjusting for model for end-stage liver disease-sodium score, mechanical ventilation, vasopressor use, renal replacement therapy, grade 3/4 hepatic encephalopathy, WBC count, and albumin. Cumulative-time-below: odds for ICU-mortality were 4%, 6%, 10%, 12%, and 12% for each-hour spent below 75, 70, 65, 60, and 55 mm Hg, respectively. In the adjusted models, significant associations only remained for mean arterial pressure less than 65 mm Hg (odds ratio, 1.07; 95% CI, 1.00-1.14; p = 0.05) and < 60 mm Hg (odds ratio, 1.10; 95% CI, 1.01-1.18; p = 0.04). CONCLUSIONS: These data suggest that maintaining a mean arterial pressure of greater than 65 mm Hg may be a reasonable target in patients with cirrhosis admitted to the ICU. However, further prospective randomized trials are needed to determine the optimal mean arterial pressure-targets in this patient population.

A roadmap to advance delirium research: Recommendations from the NIDUS Scientific Think Tank.

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference "Advancing Delirium Research: A Scientific Think Tank" in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field.

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives.

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.

The Confusion Assessment Method for the ICU-7 Delirium Severity Scale: A Novel Delirium Severity Instrument for Use in the ICU.

OBJECTIVES: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. DESIGN: Observational cohort study. SETTING: Medical, surgical, and progressive ICUs of three academic hospitals. PATIENTS: Five hundred eighteen adult (≥ 18 yr) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0-7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach's α = 0.85) and good correlation with Delirium Rating Scale-Revised-98 scores (correlation coefficient = 0.64). Known-groups validity was supported by the separation of mechanically ventilated and nonventilated assessments. Median Confusion Assessment Method for the ICU-7 scores demonstrated good predictive validity with higher odds (odds ratio = 1.47; 95% CI = 1.30-1.66) of in-hospital mortality and lower odds (odds ratio = 0.8; 95% CI = 0.72-0.9) of being discharged home after adjusting for age, race, gender, severity of illness, and chronic comorbidities. Higher Confusion Assessment Method for the ICU-7 scores were also associated with increased length of ICU stay (p = 0.001). CONCLUSIONS: Our results suggest that Confusion Assessment Method for the ICU-7 is a valid and reliable delirium severity measure among ICU patients. Further research comparing it to other delirium severity measures, its use in delirium efficacy trials, and real-life implementation is needed to determine its role in research and clinical practice.

Relationship Between African-American Race and Delirium in the ICU.

OBJECTIVES: Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors, such as age, preexisting cognitive impairment, and use of sedatives; but to date, the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. DESIGN: A prospective cohort study. SETTING: Medical and surgical ICUs of a university-affiliated, safety net hospital in Indianapolis, IN. PATIENTS: A total of 2,087 consecutive admissions with 1,008 African Americans admitted to the ICU services from May 2009 to August 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Incident delirium was defined as first positive Confusion Assessment Method for the ICU result after an initial negative Confusion Assessment Method for the ICU; and prevalent delirium was defined as positive Confusion Assessment Method for the ICU on first Confusion Assessment Method for the ICU assessment. The overall incident delirium rate in African Americans was 8.7% compared with 10.4% in Caucasians (p = 0.26). The prevalent delirium rate was 14% in both African Americans and Caucasians (p = 0.95). Significant age and race interactions were detected for incident delirium (p = 0.02) but not for prevalent delirium (p = 0.3). The hazard ratio for incident delirium for African Americans in the 18-49 years age group compared with Caucasians of similar age was 0.4 (0.1-0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. CONCLUSIONS: African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead, younger African Americans tend to have lower rates of incident delirium compared with Caucasians of similar age.

The confusion assessment method for the intensive care unit in patients with cirrhosis.

In the intensive care unit (ICU), delirium is routinely measured with the widely-used, validated Confusion Assessment Method for the ICU (CAM-ICU), but CAM-ICU has not been studied in patients with cirrhosis. We studied a group of patients with cirrhosis to determine the relationship between delirium measured by CAM-ICU and clinical outcomes. Consecutive patients with cirrhosis admitted to the ICU from 2009 to 2012 were included in a retrospective cohort study. Patients were screened twice daily for coma and delirium during their ICU stay using the Richmond Agitation Sedation Scale (RASS) and CAM-ICU. The association between delirium/coma and mortality was determined using multiple logistic regression. RASS and CAM-ICU were also compared to a retrospective assessment of hepatic encephalopathy (HE). Of 91 patients with cirrhosis, 26 (28.6 %) developed delirium/coma. RASS/CAM-ICU had fair agreement with the HE assessment (κ 0.38). Patients with delirium/coma had numerically greater mortality in-hospital (23.1 vs. 7.7 %, p = 0.07) and at 90 days (30.8 vs. 18.5 %, p = 0.26), and they also had longer hospital length of stay (median 19.5 vs. 6 days, p < 0.001). Delirium/coma was associated with increased inpatient mortality, independent of disease severity (unadjusted OR 3.6; 95 % CI, 0.99-13.1; MELD-adjusted OR 5.4; 95 % CI, 1.3-23.8; acute physiology score-adjusted OR 2.2; 95 % CI, 0.53-8.9). Delirium/coma was also associated with longer length of stay after adjusting for disease severity. In critically ill patients with cirrhosis, delirium/coma as measured by the RASS and CAM-ICU is associated with increased mortality and hospital length of stay. For these patients, these measures provide valuable information and may be useful tools for clinical care. RASS and CAM-ICU need to be compared to HE-specific measures in future studies.

Effectiveness of implementing a wake up and breathe program on sedation and delirium in the ICU.

OBJECTIVES: Mechanically ventilated critically ill patients receive significant amounts of sedatives and analgesics that increase their risk of developing coma and delirium. We evaluated the impact of a "Wake-up and Breathe Protocol" at our local ICU on sedation and delirium. DESIGN: A pre/post implementation study design. SETTING: A 22-bed mixed surgical and medical ICU. PATIENTS: Seven hundred two consecutive mechanically ventilated ICU patients from June 2010 to January 2013. INTERVENTIONS: Implementation of daily paired spontaneous awakening trials (daily sedation vacation plus spontaneous breathing trials) as a quality improvement project. MEASUREMENTS AND MAIN RESULTS: After implementation of our program, there was an increase in the mean Richmond Agitation Sedation Scale scores on weekdays of 0.88 (p < 0.0001) and an increase in the mean Richmond Agitation Sedation Scale scores on weekends of 1.21 (p < 0.0001). After adjusting for age, race, gender, severity of illness, primary diagnosis, and ICU, the incidence and prevalence of delirium did not change post implementation of the protocol (incidence: 23% pre vs 19.6% post; p = 0.40; prevalence: 66.7% pre vs 55.3% post; p = 0.06). The combined prevalence of delirium/coma decreased from 90.8% pre protocol implementation to 85% postimplementation (odds ratio, 0.505; 95% CI, 0.299-0.853; p = 0.01). CONCLUSIONS: Implementing a "Wake Up and Breathe Program" resulted in reduced sedation among critically ill mechanically ventilated patients but did not change the incidence or prevalence of delirium.

Identification of predictive patient characteristics for assessing the probability of COVID-19 in-hospital mortality.

As the world emerges from the COVID-19 pandemic, there is an urgent need to understand patient factors that may be used to predict the occurrence of severe cases and patient mortality. Approximately 20% of SARS-CoV-2 infections lead to acute respiratory distress syndrome caused by the harmful actions of inflammatory mediators. Patients with severe COVID-19 are often afflicted with neurologic symptoms, and individuals with pre-existing neurodegenerative disease have an increased risk of severe COVID-19. Although collectively, these observations point to a bidirectional relationship between severe COVID-19 and neurologic disorders, little is known about the underlying mechanisms. Here, we analyzed the electronic health records of 471 patients with severe COVID-19 to identify clinical characteristics most predictive of mortality. Feature discovery was conducted by training a regularized logistic regression classifier that serves as a machine-learning model with an embedded feature selection capability. SHAP analysis using the trained classifier revealed that a small ensemble of readily observable clinical features, including characteristics associated with cognitive impairment, could predict in-hospital mortality with an accuracy greater than 0.85 (expressed as the area under the ROC curve of the classifier). These findings have important implications for the prioritization of clinical measures used to identify patients with COVID-19 (and, potentially, other forms of acute respiratory distress syndrome) having an elevated risk of death.

Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study.

BACKGROUND: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy. OBJECTIVES: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population. METHODS: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds1) test. RESULTS: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman rs = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs = 0.61, 95%CI = [0.29, 0.81]). CONCLUSIONS: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective: To evaluate the efficacy of a post-intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants: This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention: A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures: The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results: In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, -1.06 to 4.29] for SF-36 PCS; -2.50 [95% CI, -5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance: Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03053245.

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

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

Development of a population-level prediction model for intensive care unit (ICU) survivorship and mortality in older adults: A population-based cohort study.

Background and Aims: Given the growing utilization of critical care services by an aging population, development of population-level risk models which predict intensive care unit (ICU) survivorship and mortality may offer advantages for researchers and health systems. Our objective was to develop a risk model for ICU survivorship and mortality among community dwelling older adults. Methods: This was a population-based cohort study of 48,127 patients who were 50 years and older with at least one primary care visit between January 1, 2017, and December 31, 2017. We used electronic health record (EHR) data to identify variables predictive of ICU survivorship. Results: ICU admission and mortality within 2 years after index primary care visit date were used to divide patients into three groups of "alive without ICU admission", "ICU survivors," and "death." Multinomial logistic regression was used to identify EHR predictive variables for the three patient outcomes. Cross-validation by randomly splitting the data into derivation and validation data sets (60:40 split) was used to identify predictor variables and validate model performance using area under the receiver operating characteristics (AUC) curve. In our overall sample, 92.2% of patients were alive without ICU admission, 6.2% were admitted to the ICU at least once and survived, and 1.6% died. Greater deciles of age over 50 years, diagnoses of chronic obstructive pulmonary disorder or chronic heart failure, and laboratory abnormalities in alkaline phosphatase, hematocrit, and albumin contributed highest risk score weights for mortality. Risk scores derived from the model discriminated between patients that died versus remained alive without ICU admission (AUC = 0.858), and between ICU survivors versus alive without ICU admission (AUC = 0.765). Conclusion: Our risk scores provide a feasible and scalable tool for researchers and health systems to identify patient cohorts at increased risk for ICU admission and survivorship. Further studies are needed to prospectively validate the risk scores in other patient populations.

Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study.

OBJECTIVE: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU). PATIENTS: 178 ICU patients with delirium, alive and remaining in ICU at one week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. CONCLUSION: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.

Enhancing care for hospitalized older adults with cognitive impairment: a randomized controlled trial.

BACKGROUND: Approximately 40% of hospitalized older adults have cognitive impairment (CI) and are more prone to hospital-acquired complications. The Institute of Medicine suggests using health information technology to improve the overall safety and quality of the health care system. OBJECTIVE: Evaluate the efficacy of a clinical decision support system (CDSS) to improve the quality of care for hospitalized older adults with CI. DESIGN: A randomized controlled clinical trial. SETTING: A public hospital in Indianapolis. POPULATION: A total of 998 hospitalized older adults were screened for CI, and 424 patients (225 intervention, 199 control) with CI were enrolled in the trial with a mean age of 74.8, 59% African Americans, and 68% female. INTERVENTION: A CDSS alerts the physicians of the presence of CI, recommends early referral into a geriatric consult, and suggests discontinuation of the use of Foley catheterization, physical restraints, and anticholinergic drugs. MEASUREMENTS: Orders of a geriatric consult and discontinuation orders of Foley catheterization, physical restraints, or anticholinergic drugs. RESULTS: Using intent-to-treat analyses, there were no differences between the intervention and the control groups in geriatric consult orders (56% vs 49%, P = 0.21); discontinuation orders for Foley catheterization (61.7% vs 64.6%, P = 0.86); physical restraints (4.8% vs 0%, P = 0.86), or anticholinergic drugs (48.9% vs 31.2%, P = 0.11). CONCLUSION: A simple screening program for CI followed by a CDSS did not change physician prescribing behaviors or improve the process of care for hospitalized older adults with CI.