Using phenotypic data from the Electronic Health Record (EHR) to predict discharge.

BACKGROUND: Timely discharge to post-acute care (PAC) settings, such as skilled nursing facilities, requires early identification of eligible patients. We sought to develop and internally validate a model which predicts a patient's likelihood of requiring PAC based on information obtained in the first 24 h of hospitalization. METHODS: This was a retrospective observational cohort study. We collected clinical data and commonly used nursing assessments from the electronic health record (EHR) for all adult inpatient admissions at our academic tertiary care center from September 1, 2017 to August 1, 2018. We performed a multivariable logistic regression to develop the model from the derivation cohort of the available records. We then evaluated the capability of the model to predict discharge destination on an internal validation cohort. RESULTS: Age (adjusted odds ratio [AOR], 1.04 [per year]; 95% Confidence Interval [CI], 1.03 to 1.04), admission to the intensive care unit (AOR, 1.51; 95% CI, 1.27 to 1.79), admission from the emergency department (AOR, 1.53; 95% CI, 1.31 to 1.78), more home medication prescriptions (AOR, 1.06 [per medication count increase]; 95% CI 1.05 to 1.07), and higher Morse fall risk scores at admission (AOR, 1.03 [per unit increase]; 95% CI 1.02 to 1.03) were independently associated with higher likelihood of being discharged to PAC facility. The c-statistic of the model derived from the primary analysis was 0.875, and the model predicted the correct discharge destination in 81.2% of the validation cases. CONCLUSIONS: A model that utilizes baseline clinical factors and risk assessments has excellent model performance in predicting discharge to a PAC facility.

Screening for the high-need population using single institution versus state-wide admissions discharge transfer feed.

BACKGROUND: Access to programs for high-needs patients depending on single-institution electronic health record data (EHR) carries risks of biased sampling. We investigate a statewide admission, discharge, and transfer feed (ADT) in assessing equity in access to these programs. METHODS: This is a retrospective cross-sectional study. We included high-need patients at Vanderbilt University Medical Center (VUMC) 18 years or older, with at least three emergency visits (ED) or hospitalizations in Tennessee from January 1 to June 30, 2021, including at least one at VUMC. We used the Tennessee ADT database to identify high-need patients with at least one VUMC ED/hospitalization. Then, we compared this population with high-need patients identified using VUMC's Epic® EHR database. The primary outcome was the sensitivity of VUMC-only criteria for identifying high-need patients compared to the statewide ADT reference standard. RESULTS: We identified 2549 patients with at least one ED/hospitalization and assessed them as high-need based on the statewide ADT. Of those, 2100 had VUMC-only visits, and 449 had VUMC and non-VUMC visits. VUMC-only visit screening criteria showed high sensitivity (99.1%, 95% CI: 98.7 - 99.5%), showing that the high-needs patients admitted to VUMC infrequently access alternative systems. Results showed no meaningful difference in sensitivity when stratified by patient's race or insurance. CONCLUSIONS: ADT allows examination for potential selection bias when relying upon single-institution utilization. In VUMC's high-need patients, there's minimal selection bias when depending on same-site utilization. Further research must understand how biases vary by site and durability over time.

Multicenter International Cohort Validation of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-sedation Scale.

OBJECTIVE: In a multicenter, international cohort, we aimed to validate a modified Sequential Organ Failure Assessment (mSOFA) using the Richmond Agitation-Sedation Scale, hypothesized as comparable to the Glasgow Coma Scale (GCS)-based Sequential Organ Failure Assessment (SOFA). SUMMARY BACKGROUND DATA: The SOFA score, whose neurologic component is based on the GCS, can predict intensive care unit (ICU) mortality. But, GCS is often missing in lieu of other assessments, such as the also reliable and validated Richmond Agitation Sedation Scale (RASS). Single-center data suggested an RASS-based SOFA (mSOFA) predicted ICU mortality. METHODS: Our nested cohort within the prospective 2016 Fourth International Study of Mechanical Ventilation contains 4120 ventilated patients with daily RASS and GCS assessments (20,023 patient-days, 32 countries). We estimated GCS from RASS via a proportional odds model without adjustment. ICU mortality logistic regression models and c-statistics were constructed using SOFA (measured GCS) and mSOFA (measured RASS-estimated GCS), adjusted for age, sex, body-mass index, region (Europe, USA-Canada, Latin America, Africa, Asia, Australia-New Zealand), and postoperative status (medical/surgical). RESULTS: Cohort-wide, the mean SOFA=9.4+/-2.8 and mean mSOFA = 10.0+/-2.3, with ICU mortality = 31%. Mean SOFA and mSOFA similarly predicted ICU mortality (SOFA: AUC = 0.784, 95% CI = 0.769-0.799; mSOFA: AUC = 0.778, 95% CI = 0.763-0.793, P = 0.139). Across models, other predictors of mortality included higher age, female sex, medical patient, and African region (all P < 0.001). CONCLUSIONS: We present the first SOFA modification with RASS in a "real-world" international cohort. Estimating GCS from RASS preserves predictive validity of SOFA to predict ICU mortality. Alternative neurologic measurements like RASS can be viably integrated into severity of illness scoring systems like SOFA.

Delirium's Arousal Subtypes and Their Relationship with 6-Month Functional Status and Cognition.

OBJECTIVE: We sought to determine how delirium subtyped by arousal affected 6-month function and cognition in acutely ill older patients. METHODS: This was secondary analysis of a prospective cohort study which enrolled hospitalized patients ≥65 years old. Delirium and arousal were ascertained daily in the emergency department and the first 7 days of hospitalization using the modified Brief Confusion Assessment Method and Richmond Agitation Sedation Scale, respectively. For each day, patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Preillness and 6-month functional status were determined using the Older American Resources and Services activities of daily living scale which ranges from 0 (completely dependent) to 28 (completely independent). Preillness and 6-month cognition were determined using the Informant Questionnaire on Cognitive Decline in the Elderly which ranges from 1 (markedly improved cognition) to 5 (severe cognitive impairment). Multiple linear regression was performed adjusted for preillness Older American Resources and Services activities of daily living and Informant Questionnaire on Cognitive Decline in the Elderly and other relevant confounders. RESULTS: In 228 older patients, delirium with normal arousal was the only subtype independently associated with poorer 6-month function and cognition. For every day spent in this subtype, the 6-month Older American Resources and Services activities of daily living decreased by 0.84 points (95% confidence interval: -1.59 to -0.09) and the patient's 6-month Informant Questionnaire on Cognitive Decline in the Elderly significantly increased by 0.14 points (95% confidence interval: 0.06-0.23). CONCLUSIONS: Delirium with normal arousal, as opposed to delirium with decreased or increased arousal, was the only arousal subtype significantly associated with worsening 6-month function and cognition. Subtyping delirium by arousal may have important prognostic value.

Patterns of multimorbidity associated with 30-day readmission: a multinational study.

BACKGROUND: Multimorbidity is associated with higher healthcare utilization; however, data exploring its association with readmission are scarce. We aimed to investigate which most important patterns of multimorbidity are associated with 30-day readmission. METHODS: We used a multinational retrospective cohort of 126,828 medical inpatients with multimorbidity defined as ≥2 chronic diseases. The primary and secondary outcomes were 30-day potentially avoidable readmission (PAR) and 30-day all-cause readmission (ACR), respectively. Only chronic diseases were included in the analyses. We presented the OR for readmission according to the number of diseases or body systems involved, and the combinations of diseases categories with the highest OR for readmission. RESULTS: Multimorbidity severity, assessed as number of chronic diseases or body systems involved, was strongly associated with PAR, and to a lesser extend with ACR. The strength of association steadily and linearly increased with each additional disease or body system involved. Patients with four body systems involved or nine diseases already had a more than doubled odds for PAR (OR 2.35, 95%CI 2.15-2.57, and OR 2.25, 95%CI 2.05-2.48, respectively). The combinations of diseases categories that were most strongly associated with PAR and ACR were chronic kidney disease with liver disease or chronic ulcer of skin, and hematological malignancy with esophageal disorders or mood disorders, respectively. CONCLUSIONS: Readmission was associated with the number of chronic diseases or body systems involved and with specific combinations of diseases categories. The number of body systems involved may be a particularly interesting measure of the risk for readmission in multimorbid patients.

A patient-centered deprescribing intervention for hospitalized older patients with polypharmacy: rationale and design of the Shed-MEDS randomized controlled trial.

BACKGROUND: Polypharmacy is prevalent among hospitalized older adults, particularly those being discharged to a post-care care facility (PAC). The aim of this randomized controlled trial is to determine if a patient-centered deprescribing intervention initiated in the hospital and continued in the PAC setting reduces the total number of medications among older patients. METHODS: The Shed-MEDS study is a 5-year, randomized controlled clinical intervention trial comparing a patient-centered describing intervention with usual care among older (≥50 years) hospitalized patients discharged to PAC, either a skilled nursing facility (SNF) or an inpatient rehabilitation facility (IPR). Patient measurements occur at hospital enrollment, hospital discharge, within 7 days of PAC discharge, and at 60 and 90 days following PAC discharge. Patients are randomized in a permuted block fashion, with block sizes of two to four. The overall effectiveness of the intervention will be evaluated using total medication count as the primary outcome measure. We estimate that 576 patients will enroll in the study. Following attrition due to death or loss to follow-up, 420 patients will contribute measurements at 90 days, which provides 90% power to detect a 30% versus 25% reduction in total medications with an alpha error of 0.05. Secondary outcomes include the number of medications associated with geriatric syndromes, drug burden index, medication adherence, the prevalence and severity of geriatric syndromes and functional health status. DISCUSSION: The Shed-MEDS trial aims to test the hypothesis that a patient-centered deprescribing intervention initiated in the hospital and continuing through the PAC stay will reduce the total number of medications 90 days following PAC discharge and result in improvements in geriatric syndromes and functional health status. The results of this trial will quantify the health outcomes associated with reducing medications for hospitalized older adults with polypharmacy who are discharged to post-acute care facilities. TRIAL REGISTRATION: This trial was prospectively registered at clinicaltrials.gov ( NCT02979353 ). The trial was first registered on 12/1/2016, with an update on 09/28/17 and 10/12/2018.

Preventability of Early Versus Late Hospital Readmissions in a National Cohort of General Medicine Patients.

Background: Many experts believe that hospitals with more frequent readmissions provide lower-quality care, but little is known about how the preventability of readmissions might change over the postdischarge time frame. Objective: To determine whether readmissions within 7 days of discharge differ from those between 8 and 30 days after discharge with respect to preventability. Design: Prospective cohort study. Setting: 10 academic medical centers in the United States. Patients: 822 adults readmitted to a general medicine service. Measurements: For each readmission, 2 site-specific physician adjudicators used a structured survey instrument to determine whether it was preventable and measured other characteristics. Results: Overall, 36.2% of early readmissions versus 23.0% of late readmissions were preventable (median risk difference, 13.0 percentage points [interquartile range, 5.5 to 26.4 percentage points]). Hospitals were identified as better locations for preventing early readmissions (47.2% vs. 25.5%; median risk difference, 22.8 percentage points [interquartile range, 17.9 to 31.8 percentage points]), whereas outpatient clinics (15.2% vs. 6.6%; median risk difference, 10.0 percentage points [interquartile range, 4.6 to 12.2 percentage points]) and home (19.4% vs. 14.0%; median risk difference, 5.6 percentage points [interquartile range, -6.1 to 17.1 percentage points]) were better for preventing late readmissions. Limitation: Physician adjudicators were not blinded to readmission timing, community hospitals were not included in the study, and readmissions to nonstudy hospitals were not included in the results. Conclusion: Early readmissions were more likely to be preventable and amenable to hospital-based interventions. Late readmissions were less likely to be preventable and were more amenable to ambulatory and home-based interventions. Primary Funding Source: Association of American Medical Colleges.

The Cost of ICU Delirium and Coma in the Intensive Care Unit Patient.

RATIONALE: Intensive care unit (ICU) delirium is highly prevalent and a potentially avoidable hospital complication. The current cost of ICU delirium is unknown. OBJECTIVES: To specify the association between the daily occurrence of delirium in the ICU with costs of ICU care accounting for time-varying illness severity and death. RESEARCH DESIGN: We performed a prospective cohort study within medical and surgical ICUs in a large academic medical center. SUBJECTS: We analyzed critically ill patients (N=479) with respiratory failure and/or shock. MEASURES: Covariates included baseline factors (age, insurance, cognitive impairment, comorbidities, Acute Physiology and Chronic Health Evaluation II Score) and time-varying factors (sequential organ failure assessment score, mechanical ventilation, and severe sepsis). The primary analysis used a novel 3-stage regression method: first, estimation of the cumulative cost of delirium over 30 ICU days and then costs separated into those attributable to increased resource utilization among survivors and those that were avoided on the account of delirium's association with early mortality in the ICU. RESULTS: The patient-level 30-day cumulative cost of ICU delirium attributable to increased resource utilization was $17,838 (95% confidence interval, $11,132-$23,497). A combination of professional, dialysis, and bed costs accounted for the largest percentage of the incremental costs associated with ICU delirium. The 30-day cumulative incremental costs of ICU delirium that were avoided due to delirium-associated early mortality was $4654 (95% confidence interval, $2056-7869). CONCLUSIONS: Delirium is associated with substantial costs after accounting for time-varying illness severity and could be 20% higher (∼$22,500) if not for its association with early ICU mortality.

Interventions for preventing intensive care unit delirium in adults.

BACKGROUND: Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to the environment. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium. It can profoundly affect both them and their families because it is associated with increased mortality, longer duration of mechanical ventilation, longer hospital and ICU stay and long-term cognitive impairment. It also results in increased costs for society. OBJECTIVES: To assess existing evidence for the effect of preventive interventions on ICU delirium, in-hospital mortality, the number of delirium- and coma-free days, ventilator-free days, length of stay in the ICU and cognitive impairment. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, Latin American Caribbean Health Sciences Literature, CINAHL from 1980 to 11 April 2018 without any language limits. We adapted the MEDLINE search for searching the other databases. Furthermore, we checked references, searched citations and contacted study authors to identify additional studies. We also checked the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and CenterWatch.com (all on 24 April 2018). SELECTION CRITERIA: We included randomized controlled trials (RCTs) of adult medical or surgical ICU patients receiving any intervention for preventing ICU delirium. The control could be standard ICU care, placebo or both. We assessed the quality of evidence with GRADE. DATA COLLECTION AND ANALYSIS: We checked titles and abstracts to exclude obviously irrelevant studies and obtained full reports on potentially relevant ones. Two review authors independently extracted data. If possible we conducted meta-analyses, otherwise we synthesized data narratively. MAIN RESULTS: The electronic search yielded 8746 records. We included 12 RCTs (3885 participants) comparing usual care with the following interventions: commonly used drugs (four studies); sedation regimens (four studies); physical therapy or cognitive therapy, or both (one study); environmental interventions (two studies); and preventive nursing care (one study). We found 15 ongoing studies and five studies awaiting classification. The participants were 48 to 70 years old; 48% to 74% were male; the mean acute physiology and chronic health evaluation (APACHE II) score was 14 to 28 (range 0 to 71; higher scores correspond to more severe disease and a higher risk of death). With the exception of one study, all participants were mechanically ventilated in medical or surgical ICUs or mixed. The studies were overall at low risk of bias. Six studies were at high risk of detection bias due to lack of blinding of outcome assessors. We report results for the two most commonly explored approaches to delirium prevention: pharmacologic and a non-pharmacologic intervention.Haloperidol versus placebo (two RCTs, 1580 participants)The event rate of ICU delirium was measured in one study including 1439 participants. No difference was identified between groups, (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.87 to 1.17) (moderate-quality evidence). Haloperidol versus placebo neither reduced or increased in-hospital mortality, (RR 0.98, 95% CI 0.80 to 1.22; 2 studies; 1580 participants (moderate-quality evidence)); the number of delirium- and coma-free days, (mean difference (MD) -0.60, 95% CI -1.37 to 0.17; 2 studies, 1580 participants (moderate-quality of evidence)); number of ventilator-free days (mean 23.8 (MD -0.30, 95% CI -0.93 to 0.33) 1 study; 1439 participants, (high-quality evidence)); length of ICU stay, (MD 0.18, 95% CI -0.60 to 0.97); 2 studies, 1580 participants; high-quality evidence). None of the studies measured cognitive impairment. In one study there were three serious adverse events in the intervention group and five in the placebo group; in the other there were five serious adverse events and three patients died, one in each group. None of the serious adverse events were judged to be related to interventions received (moderate-quality evidence).Physical and cognitive therapy interventions (one study, 65 participants)The study did not measure the event rate of ICU delirium. A physical and cognitive therapy intervention versus standard care neither reduced nor increased in-hospital mortality, (RR 0.94, 95% CI 0.40 to 2.20, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of delirium- and coma-free days, (MD -2.8, 95% CI -10.1 to 4.6, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of ventilator-free days (within the first 28/30 days) was median 27.4 (IQR 0 to 29.2) and 25 (IQR 0 to 28.9); 1 study, 65 participants; very low-quality evidence, length of ICU stay, (MD 1.23, 95% CI -0.68 to 3.14, I² = 0; 1 study, 65 participants; very low-quality evidence); cognitive impairment measured by the MMSE: Mini-Mental State Examination with higher scores indicating better function, (MD 0.97, 95% CI -0.19 to 2.13, I² = 0; 1 study, 30 participants; very low-quality evidence); or measured by the Dysexecutive questionnaire (DEX) with lower scores indicating better function (MD -8.76, 95% CI -19.06 to 1.54, I² = 0; 1 study, 30 participants; very low-quality evidence). One patient experienced acute back pain accompanied by hypotensive urgency during physical therapy. AUTHORS' CONCLUSIONS: There is probably little or no difference between haloperidol and placebo for preventing ICU delirium but further studies are needed to increase our confidence in the findings. There is insufficient evidence to determine the effects of physical and cognitive intervention on delirium. The effects of other pharmacological interventions, sedation, environmental, and preventive nursing interventions are unclear and warrant further investigation in large multicentre studies. Five studies are awaiting classification and we identified 15 ongoing studies, evaluating pharmacological interventions, sedation regimens, physical and occupational therapy combined or separately, and environmental interventions, that may alter the conclusions of the review in future.

The HOSPITAL Score Predicts Potentially Preventable 30-Day Readmissions in Conditions Targeted by the Hospital Readmissions Reduction Program.

BACKGROUND/OBJECTIVES: New tools to accurately identify potentially preventable 30-day readmissions are needed. The HOSPITAL score has been internationally validated for medical inpatients, but its performance in select conditions targeted by the Hospital Readmission Reduction Program (HRRP) is unknown. DESIGN: Retrospective cohort study. SETTING: Six geographically diverse medical centers. PARTICIPANTS/EXPOSURES: All consecutive adult medical patients discharged alive in 2011 with 1 of the 4 medical conditions targeted by the HRRP (acute myocardial infarction, chronic obstructive pulmonary disease, pneumonia, and heart failure) were included. Potentially preventable 30-day readmissions were identified using the SQLape algorithm. The HOSPITAL score was calculated for all patients. MEASUREMENTS: A multivariable logistic regression model accounting for hospital effects was used to evaluate the accuracy (Brier score), discrimination (c-statistic), and calibration (Pearson goodness-of-fit) of the HOSPITAL score for each 4 medical conditions. RESULTS: Among the 9181 patients included, the overall 30-day potentially preventable readmission rate was 13.6%. Across all 4 diagnoses, the HOSPITAL score had very good accuracy (Brier score of 0.11), good discrimination (c-statistic of 0.68), and excellent calibration (Hosmer-Lemeshow goodness-of-fit test, P=0.77). Within each diagnosis, performance was similar. In sensitivity analyses, performance was similar for all readmissions (not just potentially preventable) and when restricted to patients age 65 and above. CONCLUSIONS: The HOSPITAL score identifies a high-risk cohort for potentially preventable readmissions in a variety of practice settings, including conditions targeted by the HRRP. It may be a valuable tool when included in interventions to reduce readmissions within or across these conditions.

Exploring Delirium's Heterogeneity: Association Between Arousal Subtypes at Initial Presentation and 6-Month Mortality in Older Emergency Department Patients.

OBJECTIVES: To determine how delirium subtyped by level of arousal at initial presentation affects 6-month mortality. DESIGN: This was a preplanned secondary analysis of two prospective cohort studies. SETTING: Academic tertiary care emergency department (ED). PARTICIPANTS: 1,084 ED patients who were 65 years old or older. MEASUREMENTS: At the time of enrollment, trained research personnel performed the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation Sedation Score to determine delirium and level of arousal, respectively. Patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Death was ascertained by medical record review and the Social Security Death Index. Cox proportional hazard regression was used to analyze the association between delirium arousal subtypes and 6-month mortality. RESULTS: Delirium with normal arousal was the only subtype that was significantly associated with increased 6-month mortality (hazard ratio [HR]: 3.1, 95% confidence interval [CI]: 1.3-7.4) compared with the no delirium group after adjusting for confounders. The HRs for delirium with decreased and increased arousal were 1.4 (95% CI: 0.9-2.1) and 1.3 (95% CI: 0.3-5.4), respectively. CONCLUSIONS: Delirious ED patients with normal arousal at initial presentation had a threefold increased hazard of death within 6 months compared with patients without delirium. There was a trend towards increased hazard of death in delirious ED patients with decreased arousal, but this relationship did not reach statistical significance. These data suggest that subtyping delirium by arousal may have prognostic value but requires confirmation with a larger study.

Reducing hospital readmission rates: current strategies and future directions.

New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel.

Validity of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-Sedation Scale.

OBJECTIVES: The Sequential Organ Failure Assessment and other severity of illness scales rely on the Glasgow Coma Scale to measure acute neurologic dysfunction, but the Glasgow Coma Scale is unavailable or inconsistently applied in some institutions. The objective of this study was to assess the validity of a modified Sequential Organ Failure Assessment that uses the Richmond Agitation-Sedation Scale instead of Glasgow Coma Scale. DESIGN: Prospective cohort study. SETTING: Medical and surgical ICUs within a large, tertiary care hospital. PATIENTS: Critically ill medical/surgical ICU patients. INTERVENTIONS: We calculated daily Sequential Organ Failure Assessment scores by using electronic medical record-derived data. By using bedside nurse-recorded Glasgow Coma Scale and Richmond Agitation-Sedation Scale measures, we calculated neurologic Sequential Organ Failure Assessment scores using the original Glasgow Coma Scale-based approach and a novel Richmond Agitation-Sedation Scale-based approach, converting the 10-point Richmond Agitation-Sedation Scale to a 4-point neurologic Sequential Organ Failure Assessment score. We assessed construct validity of Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment by analyzing correlations with established severity of illness constructs (Acute Physiology and Chronic Health Evaluation II and Glasgow Coma Scale-based Sequential Organ Failure Assessment) and predictive validity by using logistic regression to determine whether Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment predicts ICU, hospital, and 1-year mortality. We assessed discriminative performance with c-statistics. MEASUREMENTS AND MAIN RESULTS: Among 513 patients (5,199 patient-days), Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment was strongly correlated with Acute Physiology and Chronic Health Evaluation II acute physiology score at enrollment (r = 0.583; 95% CI, 0.518-0.642) and daily Glasgow Coma Scale-based Sequential Organ Failure Assessment scores (r = 0.963; 95% CI, 0.956-0.968). Mean Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment scores predicted ICU mortality (areas under the curve = 0.814)-as did mean Glasgow Coma Scale-based Sequential Organ Failure Assessment (0.799)-as well as hospital and 1-year mortality. Admission Sequential Organ Failure Assessment scores, whether using Richmond Agitation-Sedation Scale or Glasgow Coma Scale, were less accurate predictors of mortality; areas under the curves for ICU mortality for Richmond Agitation-Sedation Scale-based and Glasgow Coma Scale-based Sequential Organ Failure Assessment, for example, were 0.622 and 0.608, respectively. CONCLUSION: A modified Sequential Organ Failure Assessment score that uses bedside Richmond Agitation-Sedation Scale when Glasgow Coma Scale data are not available is a valid means of assessing daily severity of illness in the ICU and may be valuable for risk-adjustment and benchmarking purposes.

Population Pharmacokinetics of Fentanyl in the Critically Ill.

OBJECTIVE: To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. DESIGN: Prospective cohort study. SETTING: Medical and surgical ICUs in a large tertiary care hospital in the United States. PATIENTS: Patients with acute respiratory failure and/or shock who received fentanyl during the first 5 days of their ICU stay. MEASUREMENTS AND MAIN RESULTS: We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to 5 days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 µg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found that fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance, intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 L/hr (95% CI, 32-39 L/hr), 55 L/hr (95% CI, 42-68 L/hr), 203 L (95% CI, 140-266 L), and 523 L (95% CI, 428-618 L), respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart diseases were included. CONCLUSIONS: In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients.

A Review of Multifaceted Care Approaches for the Prevention and Mitigation of Delirium in Intensive Care Units.

OBJECTIVE: The objective of this review is to examine the effectiveness, implementation, and costs of multifaceted care approaches, including care bundles, for the prevention and mitigation of delirium in patients hospitalized in intensive care units (ICUs). DATA SOURCES: A systematic search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted utilizing PubMed, EMBASE, and CINAHL. Searches were limited to studies published in English from January 1, 1988, to March 31, 2014. Randomized controlled trials and comparative studies of multifaceted care approaches with the reduction of delirium in ICU patients as an outcome and evaluations of the implementation or cost-effectiveness of these interventions were included. DATA EXTRACTION: Data on study methods including design, cohort size, interventions, and outcomes were abstracted, reviewed, and summarized. Given the variability in study design, populations, and interventions, a qualitative review of findings was conducted. DATA SYNTHESIS: In all, 14 studies met our inclusion criteria: 6 examined outcomes, 5 examined implementation, 2 examined outcomes and implementation, and 1 examined cost-effectiveness. The majority of studies indicated that multifaceted care approaches were associated with improved patient outcomes including reduced incidence and duration of delirium. Additionally, improvements in functional status and reductions in coma and ventilator days, hospital length of stay, and/or mortality rates were observed. Implementation strategies included structured quality improvement approaches with ongoing audit and feedback, multidisciplinary care teams, intensive training, electronic reporting systems, and local support teams. The cost-effectiveness analysis indicated an average reduction of $1000 in hospital costs for patients treated with a multifaceted care approach. CONCLUSION: Although multifaceted care approaches may reduce delirium and improve patient outcomes, greater improvements may be achieved by deploying a comprehensive bundle of care practices including awakening and breathing trials, delirium monitoring and treatment, and early mobility. Further research to address this knowledge gap is essential to providing best care for ICU patients.

Methods to identify saline-contaminated electrolyte profiles.

BACKGROUND: With providers becoming more selective in ordering daily chemistry profiles, it is critical that profiles ordered are accurate. Contaminated electrolyte profiles are an overlooked and potentially dangerous source of inaccurate clinical data. This study aimed to develop a method to accurately identify electrolyte profiles contaminated with normal saline to prevent reporting of erroneous measurements. METHODS: We conducted a retrospective cohort study of 76,497 electrolyte profiles from 5032 patients in a deidentified clinical database of all patients in the electronic medical record at Vanderbilt University Medical Center. Five methods to identify errors in quantification based on either deviations from observed concentration distributions or expected numerical changes from saline contamination were developed and tested. Potentially contaminated measurements were validated based on changes in electrolyte concentrations observed in the subsequent sample. RESULTS: Identification of erroneous electrolyte profiles based on absolute and percent deviations from normal variation rarely resulted in >50% of identified samples validated as contaminated. A targeted methodology based on expected changes in calcium and chloride concentrations due to saline contamination validated approximately 80% of identified samples when higher thresholds for changes in electrolyte concentration were used and 50% of identified samples when lower thresholds were used. CONCLUSIONS: Targeted methodology based on changes in chloride and calcium successfully identified electrolyte profiles suspicious for contamination. Implementation of this methodology could prevent misinterpretation of a patient's clinical course, inappropriate interventions, and unwarranted changes in treatment strategy.

Statins and delirium during critical illness: a multicenter, prospective cohort study.

OBJECTIVE: Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium. DESIGN: Multicenter, prospective cohort study. SETTING: Medical and surgical ICUs in two large tertiary care hospitals in the United States. PATIENTS: Patients with acute respiratory failure or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51-70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19-31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10-0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46-1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35-1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44-1.66; p = 0.18), yet the longer a prehospital statin user's statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions). CONCLUSIONS: In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.

Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle.

OBJECTIVE: The debilitating and persistent effects of ICU-acquired delirium and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate the effectiveness and safety of implementing the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle into everyday practice. DESIGN: Eighteen-month, prospective, cohort, before-after study conducted between November 2010 and May 2012. SETTING: Five adult ICUs, one step-down unit, and one oncology/hematology special care unit located in a 624-bed tertiary medical center. PATIENTS: Two hundred ninety-six patients (146 prebundle and 150 postbundle implementation), who are 19 years old or older, managed by the institutions' medical or surgical critical care service. INTERVENTIONS: Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle. MEASUREMENTS AND MAIN RESULTS: For mechanically ventilated patients (n = 187), we examined the association between bundle implementation and ventilator-free days. For all patients, we used regression models to quantify the relationship between Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle implementation and the prevalence/duration of delirium and coma, early mobilization, mortality, time to discharge, and change in residence. Safety outcomes and bundle adherence were monitored. Patients in the postimplementation period spent three more days breathing without mechanical assistance than did those in the preimplementation period (median [interquartile range], 24 [7-26] vs 21 [0-25]; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity, and mechanical ventilation status, patients managed with the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle experienced a near halving of the odds of delirium (odds ratio, 0.55; 95% CI, 0.33-0.93; p = 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (odds ratio, 2.11; 95% CI, 1.29-3.45; p = 0.003). No significant differences were noted in self-extubation or reintubation rates. CONCLUSIONS: Critically ill patients managed with the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle spent three more days breathing without assistance, experienced less delirium, and were more likely to be mobilized during their ICU stay than patients treated with usual care.

Road map to a patient-centered research agenda at the intersection of hospital medicine and geriatric medicine.

As the United States ages, the patient population in acute care hospitals is increasingly older and more medically complex. Despite evidence of a high burden of disease, high costs, and often poor outcomes of care, there is limited understanding of the presentation, diagnostic strategies, and management of acute illness in older adults. In this paper, we present a strategy for the development of a research agenda at the intersection of hospital and geriatric medicine. This approach is informed by the Patient-Centered Outcomes Research Institute (PCORI) framework for identification and prioritization of research areas, emphasizing input from patients and caregivers. The framework's four components are: 1) Topic generation, 2) Gap Analysis in Systematic Review, 3) Value of information (VOI) analysis, and 4) Peer Review. An inclusive process for topic generation requiring the systematic engagement of multiple stakeholders, especially patients, is emphasized. In subsequent steps, researchers and stakeholders prioritize research topics in order to identify areas that optimize patient-centeredness, population impact, impact on clinical decision making, ease of implementation, and durability. Finally, next steps for dissemination of the research agenda and evaluation of the impact of the patient-centered research prioritization process are described.