Affiliations
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Email
ed.vasilevskis@vanderbilt.edu
Given name(s)
Eduard E.
Family name
Vasilevskis
Degrees
MD, MPH

MAGS Prevalence in Older Adults

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Medications associated with geriatric syndromes and their prevalence in older hospitalized adults discharged to skilled nursing facilities

Geriatric syndromes are common clinical conditions in older adults that do not fall into specific disease categories. Unlike the traditional definition of a syndrome, geriatric syndrome refers to a condition that is mediated by multiple shared underlying risk factors.[1, 2] Conditions commonly referred to as geriatric syndromes include delirium, cognitive impairment, falls, unintentional weight loss, depressive symptoms, and incontinence. Even though many perceive it as medical misnomer,[3] geriatric syndromes have been shown to negatively impact quality of life and activities of daily living in older adults.[2] They are also associated with adverse outcomes such as increased healthcare utilization, functional decline, and mortality, even after adjusting for age and disease severity.[4, 5, 6] Hospitalized older adults, including those discharged to skilled nursing facilities (SNFs)[7, 8] are particularly at high risk for new‐onset or exacerbation of geriatric syndromes and poor outcomes.[7, 9, 10] However, hospital providers seldom assess, manage, or document geriatric syndromes because they are often overshadowed by disease conditions that lead to an acute episode requiring hospitalization (e.g., heart disease).[11]

Pharmacotherapy is the cornerstone of hospital treatment, and it is well‐known that it affects multiple physiologic systems causing side effects apart from the condition they are approved to treat. Given that geriatric syndromes are a result of impairments in multiple organ systems, it is plausible that pharmacotherapy may initiate or worsen these syndromes.[12] Medication‐related problems in older adults are well known. Polypharmacy and adverse drug events (as a result of drug‐drug/disease interactions and changes in pharmacokinetics and pharmacodynamics) are prevalent in multimorbid elderly patients.[13, 14, 15, 16] The prescribing cascade[17] increases the medication burden and may be a contributing factor for geriatric syndromes in hospitalized patients.[18] For instance, laxatives may be prescribed to counteract constipation caused by anticholinergic drugs.

The American Geriatric Society (AGS) Beers list[19, 20] and similar criteria[21] provide excellent resources to identify medications with potentially harmful interactions or adverse effects in older adults. Although these lists include medicines associated with a specific geriatric syndrome, they were not developed to explicitly link medicines across multiple geriatric syndromes, regardless of indication or appropriateness. For example, medications that effect important geriatric syndromes like unintentional weight/appetite loss, depression, and urinary incontinence are not extensively covered. In addition, disease‐appropriate medications (eg, ‐blockers for systolic heart failure), that may be associated with a geriatric syndrome (eg, falls) are not included; however, they may be important to consider for a patient and clinician who are weighing the disease benefits compared to the geriatric syndrome‐related risks. Finally, the AGS 2015 Beers criteria panel mentions the limitation that many medication associations may be excluded because older adults are less represented in clinical trials.[20] Clinicians are currently limited in identifying medications potentially contributing to a broad set of geriatric syndromes in their patients without a specific list of medications associated with geriatric syndromes (MAGS).[20]

In response to this gap, identifying these medications is important and should be a starting point in efforts toward prevention and treatment of geriatric syndromes. The 2 main objectives of this study were to first identify medications that may meaningfully contribute to 6 geriatric syndromes and subsequently describe the frequency of these medications in a population transitioning from acute care to postacute care to highlight the need and potential impact of such a list.

METHODS

This study included 2 phases that aligned with our 2 primary objectives. Phase 1 involved identifying medications associated with 6 geriatric syndromes, and phase 2 included a cross‐sectional analysis of the prevalence of these medications in a sample of patients discharged to SNFs.

Phase 1: Development of the MAGS List

Figure 1 depicts the underlying conceptual model and approach that was used in phase 1. The interaction between the patient factors and medication leads to polypharmacy that contributes to geriatric syndromes and additional adverse outcomes. As a starting point for mitigating geriatric syndromes, we used an iterative analytical process to identify a list of medications associated with the following geriatric syndromes that were documented to be highly prevalent in patients discharged to SNFs: cognitive impairment, delirium, falls, unintentional weight and/or appetite loss, urinary incontinence, and depression.[8] To be inclusive and sensitive, our approach differed from traditional systematic reviews, and in fact was meant to bring together much of the established systematic literature about disparate geriatric syndromes in 1 place, because patients often do not experience a geriatric syndrome in isolation, but rather experience multiple geriatric syndromes.[8] The MAGS list had 3 main inclusion criteria (Figure 1): (1) evidence in the published literature (systematic reviews, cohort studies, randomized clinical trials) that the medication is related to the syndrome, (2) expert panel opinion, and (3) drug databases (Lexicomp Online database[22] and/or US Food and Drug Administration [FDA]approved package inserts).[23] We generated an initial list of medications based on these 3 main criteria to identify medications with significant associations to each geriatric syndrome. The list was further expanded and vetted using an iterative review of each medication list as it related to each geriatric syndrome through a series of group meetings focused around each geriatric syndrome. Following further discussion, we obtained agreement among all team members for medications included in the final list. For each geriatric syndrome, we excluded medications from consideration if they were used to treat the same geriatric syndrome (eg, ‐adrenergic blockers used to treat incontinence in men were listed as associated with incontinence only in women). We classified medications according to the Established Pharmacologic Class available at the FDA website. We also compared our final MAGS list with the 2015 AGS Beer's list[20] by identifying medications that were related to the 6 geriatric syndromes. This included Beers[20]‐cited rationale of anticholinergic, extrapyramidal symptoms, orthostatic hypotension (eg, falls), high‐risk adverse central nervous system effects, sedating, cognitive decline (eg, antipsychotics), delirium, falls, fractures, incontinence, and gastrointestinal (eg, nausea, vomiting). Specifically, we assessed whether the medications were included as inappropriate by the AGS Beers 2015[20] list and also whether they documented the syndrome association for that medication.

Figure 1
Conceptual model and approach for development of the medication associated with geriatric syndromes (MAGS) list (phase 1).

Phase 2: Prevalence of MAGS in Hospitalized Older Adults Discharged to SNFs

Sample

We next applied the MAGS list to a convenience sample of hospitalized patients discharged to SNFs to assess the prevalence of MAGS in this sample, and also to compare with the prevalence of Beers criteria[20] medications. Our sample was selected from data collected as part of a quality‐improvement project to reduce hospital readmissions in patients discharged to SNFs. The larger study enrolled a total 1093 medical and surgical patients who had Medicare insurance eligibility and were discharged from 1 large university hospital to 23 area SNFs from January 17, 2013 through July 31, 2014. The university institutional review board waived the requirement for written consent. For the purpose of this substudy. we selected the first 154 patients with complete chart abstraction (approximately 15% of the total) as a convenience sample.

Data Analysis

We applied descriptive statistics to summarize demographic and clinical characteristics of the convenience sample. To understand potential selection biases that could have resulted by the convenience sampling, we compared participant characteristics of the convenience sample (N = 154) with the characteristics of the remaining participants of the larger study (N = 939) using independent sample t tests and 2 tests for continuous and categorical measures, respectively. We applied the MAGS list and the AGS 2015 Beers criteria[20] for the sample of 154 and identified the medications associated with each of the 6 geriatric syndromes from the discharge medication lists completed by hospital clinical pharmacists. For each patient, we identified both scheduled and PRN (pro re nata, or as needed) medications associated with each geriatric syndrome. Thereafter, we determined whether the discharge list contained at least 1 medication associated with a geriatric syndrome per the MAGS list and the AGS Beers 2015 criteria,[20] and the percentage of overall medications that were part of the MAGS and Beers lists. Data were aggregated using means and standard deviations across syndromes (ie, number of discharge medications per syndrome per patient) along with the percentage of patients with 1 or more medications related to a specific syndrome and the percentage of medications that were MAGS. All analyses were performed using the SPSS statistical package (IBM SPSS Statistics for Windows, version 23.0; IBM, Armonk, NY).

RESULTS

Phase 1: MAGS List

The iterative process applied in this analysis generated a list of 513 medications associated with the 6 geriatric syndromes. The list of medications related to each syndrome and the corresponding rationale and relevant references for their inclusion is presented in the Supporting Information, Appendix 1, in the online version of this article. Table 1 summarizes these medications across 18 major drug categories. Antiepileptics were linked to all 6 geriatric syndromes, whereas antipsychotics, antidepressants, antiparkinsonism, and opioid agonists were associated with 5 syndromes. Ten of the 18 categories were associated with 3 geriatric syndromescognitive impairment, delirium, and falls. Four medication categories were associated with only 1 syndrome. Nonopioid/nonsteroidal anti‐inflammatory and/or analgesics and nonopioid cough suppressant and expectorant medications were associated with falls syndrome only. Hormone replacement medications were associated with depression only, and immunosuppressants were associated with unintentional weight and appetite loss only.

Summary of Medications Associated With Geriatric Syndromes
Major Medication Category Delirium Cognitive Impairment Falls Unintentional Weight and Appetite Loss Urinary Incontinence Depression Drug Class/Drug Within Each Category
  • NOTE: Associated syndrome checked if at least 2 or more medications within the wider class are associated with the syndrome. Abbreviations: NSAIDs, nonsteroidal anti‐inflammatory drugs.

Antipsychotics Atypical and typical antipsychotics, buspirone
Antidepressants Tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitor, aminoketone
Antiepileptics Antiepileptics, mood stabilizers, barbiturates
Antiparkinsonism Aromatic amino acid decarboxylation inhibitor and catechol‐o‐methyltransferase inhibitor, catecholamine‐depleting sympatholytic, catechol‐o‐methyltransferase inhibitor, dopaminergic agonist, ergot derivative, monoamine oxidase inhibitor, nonergot dopamine agonist,
Benzodiazapines Benzodiazapines only
Nonbenzodiazepine hypnotics Benzodiazepine analogs, nonbenzodiazepine hypnotics, tranquilizers, ‐aminobutyric acid A receptor agonist
Opioid agonists Full or partial opioid agonists, opiates, opioids
Nonopioid/nonsteroidal anti‐inflammatory and/or analgesics Nonopioid analgesics, NSAIDs, COX‐2 selective inhibitor NSAIDs
Antihypertensives Calcium channel blocker, ‐adrenergic blocker, angiotensin‐converting enzyme inhibitor, angiotensin 2 receptor blocker, ‐adrenergic blocker, diuretics (loop, potassium sparing, thiazide), nitrate vasodilators, aldosterone blocker
Antiarrhythmic Antiarrhythmics, cardiac glycosides
Antidiabetics Insulin and insulin analogs, sulfonylureas, ‐glucosidase inhibitor, amylin analog, biguanide, glinide, GLP‐1 receptor agonist, glucagon‐like peptide‐1 agonist
Anticholinergics and/or antihistaminics Anticholinergics, histamine receptor antagonists, muscarininc antagonists, combined anticholinergics, and histamine receptor antagonists
Antiemetics Antiemetics, dopaminergic antagonists, dopamine‐2 receptor antagonist
Hormone replacement Corticosteroids, progestin, estrogen, estrogen agonist/antagonist, gonadotropin releasing hormone receptor agonist
Muscle relaxers Muscle relaxers
Immunosuppressants Calcineurin inhibitor immunosuppressant, folate analog metabolic inhibitor, purine antimetabolite
Nonopioid cough suppressants and expectorants Expectorant, non‐narcotic antitussive, ‐1 agonist, uncompetitive N‐methyl‐D‐aspartate receptor antagonist
Antimicrobials Macrolide, cephalosporin, penicillin class, rifamycin, non‐nucleoside analog reverse transcriptase inhibitor, influenza A M2 protein inhibitor
Others ‐3‐adrenergic agonist, methylxanthine, cholinesterase inhibitor, interferon and , partial cholinergic nicotinic agonist, tyrosine hydroxylase, retinoid, serotonin‐1b and serotonin‐1d receptor agonist, stimulant laxative, vitamin K antagonist, platelet aggregation inhibitor

Approximately 58% of the medications overlapped with the AGS 2015 Beer's Criteria[20] irrespective of whether the specific syndrome association was stated in the rationale.[20] Medications that overlapped were mostly in the delirium, cognitive impairment, and falls category with only a few overlaps in depression, unintentional weight loss, and urinary incontinence lists (see Supporting Information, Appendix 1, in the online version of this article).

Phase 2: Prevalence of MAGS

Among 154 participants, the mean age was 76.5 (10.6) years, 64.3% were female, 77.9% were white, and 96.1% non‐Hispanic. The median hospital length of stay was 6 days, with an interquartile range of 5 days. The orthopedic service discharged the highest proportion of patients (24%), followed by the geriatrics and internal medicine services, which each discharged 19.5% of the patients (Table 2). The remaining participants of the larger quality‐improvement project (N = 939) did not significantly differ on these demographic and clinical characteristics except for hospital length of stay, which was shorter in the sample analyzed (see Supporting Information, Appendix 2, in the online version of this article).

Baseline Characteristics for a Sample of 154 Medicare InsuranceEligible Patients Discharged to Skilled Nursing Facilities (N = 154)
Baseline Characteristics Mean ( SD) or Percent (n)
  • NOTE: Abbreviations: IQR, interquartile range; SD, standard deviation.

Age, y 76.5 ( 10.6)
Sex
Female 64.3% (99)
Race
White 77.9% (126)
Black 16.2% (25)
Unknown 0.6% (1)
Declined 0.6% (1)
Missing 0.6% (1)
Ethnicity
Non‐Hispanic 96.1% (148)
Hispanic 1.3% (2)
Unknown 2.6% (4)
Hospital length of stay, d 7.0 ( 4.2)
Hospital length of stay, d, median (IQR) 6.0 (5.0)
No. of hospital discharge medications, count 14.0 ( 4.7)
Discharge service
Orthopedic service 24.0% (37)
Geriatric service 19.5% (30)
Internal medicine 19.5% (30)
Other 37.0% (57)

Patients were discharged to SNFs with an average of 14.0 (4.7) medication orders. Overall, 43% (13%) of these discharge medication orders were MAGS. Every patient in the sample was ordered at least 1 medication associated with geriatric syndromes. Multiple MAGS were the norm, with an average of 5.9 (2.2) MAGS per patient. MAGS were also the norm, as 98.1% of the sample had medication orders associated with at least 2 different syndromes.

When the Beer's criteria[20] were applied to the medication orders (instead of the MAGS list), problematic medications appeared less common. Patients had an average of 3.04 (1.7) MAGS that were also listed on the AGS 2015 Beer's list,[20] representing an average of 22.3% of all discharge orders.

Table 3 illustrates the average number of medications per patient associated with each syndrome, and the percentage of patients (number in parentheses) discharged with at least 1 medication associated with each syndrome per the MAGS list and the Beers 2015 criteria.[20] For example, per the MAGS list, the syndrome most frequently associated with medications was falls, with patients discharged on an average of 5.5 (2.2) medications associated with falls, and 100% of the sample had at least 1 discharge medication associated with falls. Alternatively, the syndrome associated with the lowest frequency of medications was unintentional weight loss (with an average of 0.38 medications per patient), although 36% of these patients had more than 1 discharge medication associated with weight loss. As seen in Table 3, the mean and prevalence of 1 or more medications associated with each of the geriatric syndromes as identified by the Beers 2015 criteria[20] was lower than those identified by the MAGS list developed for this study.

Prevalence of Medications Associated With Geriatric Syndromes per MAGS and AGS Beers 2015 Criteria in an Older Cohort of Hospitalized Patients Discharged to Skilled Nursing Facilities (N = 154)
Geriatric Syndromes Associated Medications per MAGS List Associated Medications per AGS Beers 2015 Criteria
Mean SD Percentage of Patients Receiving 1 Related Medication Mean SD Percentage of Patients Receiving 1 Related Medication
  • NOTE: Abbreviations: AGS, American Geriatric Society; MAGS, Medications Associated With Geriatric Syndromes, SD, standard deviation.

Cognitive impairment 1.8 ( 1.2) 84.4% (130) 1.6 ( 1.2) 78.6% (121)
Delirium 1.4 ( 1.1) 76.0% (117) 1.3 ( 1.2) 68.2% (105)
Falls 5.5 ( 2.2) 100% (154) 2.6 ( 1.6) 92.2% (142)
Unintentional weight and/or appetite loss 0.4 ( 0.5) 36.3% (56) 0.1 ( 0.3) 6.5% (10)
Urinary incontinence 1.6 ( 1.0) 85.7% (132) 0.1 ( 0.2) 5.8% (9)
Depression 1.7 ( 1.0) 90.9% (140) 0.0 ( 0.0) 0.0% (0)
All syndromes 5.9 ( 2.2) 100% (154) 3.0 ( 1.7) 95% (149)

DISCUSSION

An iterative process of evidence review by a multidisciplinary panel resulted in a list of 513 medications associated with 6 common geriatric syndromes. This analysis demonstrated that hospitalized, older patients discharged to SNFs were frequently prescribed MAGS. The rate of prescribing ranged from 100% of patients with a medication associated with falls to 36% for unintentional weight loss. Moreover, an alarming 43% of all medications at hospital discharge were MAGS. For this vulnerable population, the combination of high prevalence of MAGS and high risk of geriatric syndromes emphasize a need to critically review the risks and benefits of MAGS throughout hospitalization and at the time of discharge.

A body of evidence demonstrates that many drugs in a typical older adult regimen have no specific clinical indication, are considered inappropriate, or have uncertain efficacy in the geriatric population.[24, 25, 26] This study builds on the foundational work described in landmark reviews such as the AGS Beers[20] and STOPP/START[21] (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions/Screening Tool to Alert doctors to Right, i.e. appropriate indicated Treatment) criteria. Both of these tools, however, were specifically designed as screening tools to identify medications considered unsafe for older adults under most circumstances and within specific illness states.[19, 20, 21] They are most often utilized when starting a medication to avoid acute adverse events. In contrast, the MAGS list was developed to be inclusive of medications that are often appropriate for many medical diagnoses but may also contribute to underlying geriatric syndromes that are more chronic in nature. In addition, inclusion of such medicines increases the sensitivity of screening for medications that can be targeted through patient‐centered deprescribing efforts when clinically appropriate.

A major strength of this study is that we bring together evidence across a spectrum of geriatric syndromes commonly experienced by hospitalized elders. In addition to evaluating multiple syndromes, we applied multiple modalities; particularly the use of an iterative review process by a multidisciplinary team of experts and using Lexicomp and FDA insert packages for linking medications to specific geriatric conditions. The inclusion criteria were broadened beyond single sources of evidence in an effort to capture a comprehensive list of medications. As a result, the MAGS list can be implemented as a screening tool for deprescribing interventions and assessing medication appropriateness to address individual or clusters of geriatric syndromes within a patient.

In addition to expanding this knowledge base, clinical relevance of the MAGS list is highlighted by its application to a sample of hospitalized older adults discharged to SNFs, a cohort known to experience geriatric syndromes. In fact, 43% of patients' medications at hospital discharge were MAGS. Importantly, due to the cross‐sectional nature of this study, we cannot be certain if the medication caused or potentiated each of the geriatric syndromes. However, hospitals and SNFs are devoting major resources toward reduction of falls, avoidance of urinary catheter use, and reduction of preventable readmissions. These efforts can be complemented by considering the number of medications associated with falls, urinary incontinence, and overall MAGS burden. The striking prevalence of MAGS demonstrates a rigorous need to weigh the risks and benefits of these medications. Above all, the intent of this study is not to propose that any MAGS be reflexively stopped, but rather that the MAGS list should facilitate a holistic approach to care for the complex older adult. For example, standard therapies such as gabapentin may be appropriate for treating neuralgic pain but may also contribute to falls and urinary incontinence. Thus, alternative pain treatments could be selected in place of gabapentin for a 75‐year old patient who is experiencing recurrent falls and increasing incontinence. Therefore, the MAGS list enables a patient‐provider discussion wherein medications' therapeutic benefits can be weighed against risks posed by specific clusters of geriatric syndromes, potential impact on quality of life, and consistency with goals of care.

This study has some limitations. First, although we examined a broad number of geriatric syndromes, several other geriatric syndromes experienced by hospitalized older adults were not addressed including: fecal incontinence, insomnia, and functional impairment. These syndromes were intentionally excluded from the study a priori due to reasons of feasibility and scope. Second, unlike the Beer's 2015 criteria, the MAGS list does not sub‐classify associations of medications with geriatric syndromes for patients with specific diseases (eg, heart failure). In fact, our MAGS list included medications often indicated in treating these diagnoses. A clinician must work with the patient to weigh the disease‐specific benefits of some medications with the potential effect on geriatric syndrome symptoms and outcomes. Third, the instrument has a very high sensitivity, which was intended to generate an inclusive list of medications that enables providers to weigh risks of geriatric syndromes with the intended indication benefit. The objective is not to use this list as a reflexive tool but rather help clinicians identify a starting point to address geriatric syndromes in their patients to make patient‐centered medication decisions. Although the MAGS list is intentionally large (sensitive), the advent of advanced bioinformatics can enable MAGS to be assessed in the future for both clinical and research purposes. Fourth, FDA insert packages and Lexicomp databases report anything experienced by the patient while on the particular medication, but it might not necessarily imply a causative link. The high use of MAGS and the specific geriatric syndrome may coexist due to the high prevalence and interplay of multimorbidity, polypharmacy, and geriatric syndromes in this population. Last, the list was developed by expert panel members predominantly from a single institution, which may introduce bias. Despite these limitations, the prevalence of these medications in a sample of patients transitioning from acute to postacute care highlights the utility of the MAGS list in future clinical research and quality improvement endeavors.

In conclusion, the MAGS list provides a comprehensive and sensitive indicator of medications associated with any of 6 geriatric syndromes regardless of medication indication and appropriateness. The MAGS list provides an overall degree of medication burden with respect to geriatric syndromes and a foundation for future research to assess the relationship between the presence of geriatric syndromes and syndrome‐associated medications. The MAGS list is an important first step in summarizing the data that link medications to geriatric syndromes. Future studies are needed to broaden the analysis of MAGS for other common geriatric syndromes and to identify new and emerging medications not present during the time of this analysis. The MAGS list has the potential to facilitate deprescribing efforts needed to combat the epidemic of overprescribing that may be contributing to the burden of geriatric syndromes among older patients.

Acknowledgements

The authors thank Dr. Linda Beuscher, Dr. Patricia Blair Miller, Dr. Joseph Ouslander, Dr. William Stuart Reynolds, and Dr. Warren Taylor for providing their expertise and participating in the expert panel discussions that facilitated the development of the MAGS list. The authors also recognize the research support provided by Christopher Simon Coelho.

Disclosures: This research was supported by the Department of Health and Human Services, Centers for Medicare & Medicaid Services grant #1C1CMS331006 awarded to Principal Investigator, John F. Schnelle, PhD. Dr. Vasilevskis was supported by the National Institute on Aging of the National Institutes of Health award K23AG040157 and the Geriatric Research, Education and Clinical Center. Dr. Bell was supported by National Institute on Aging‐K award K23AG048347‐01A1. Dr. Mixon is supported by a Veterans Affairs Health Services Research & Development Career Development Award (12‐168). This research was also supported by the National Center for Advancing Translational Sciences Clinical and Translational Science award UL1TR000445. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the US Department of Health and Human Services or any of its agencies, the National Center for Advancing Translation Science, the National Institutes of Health, or the Department of Veterans Affairs. Each coauthor contributed significantly to the manuscript. Dr. Kripalani has received stock/stock options from Bioscape Digital, LLC. None of the other authors have significant conflicts of interest to report related to this project or the results reported within this article.

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Geriatric syndromes are common clinical conditions in older adults that do not fall into specific disease categories. Unlike the traditional definition of a syndrome, geriatric syndrome refers to a condition that is mediated by multiple shared underlying risk factors.[1, 2] Conditions commonly referred to as geriatric syndromes include delirium, cognitive impairment, falls, unintentional weight loss, depressive symptoms, and incontinence. Even though many perceive it as medical misnomer,[3] geriatric syndromes have been shown to negatively impact quality of life and activities of daily living in older adults.[2] They are also associated with adverse outcomes such as increased healthcare utilization, functional decline, and mortality, even after adjusting for age and disease severity.[4, 5, 6] Hospitalized older adults, including those discharged to skilled nursing facilities (SNFs)[7, 8] are particularly at high risk for new‐onset or exacerbation of geriatric syndromes and poor outcomes.[7, 9, 10] However, hospital providers seldom assess, manage, or document geriatric syndromes because they are often overshadowed by disease conditions that lead to an acute episode requiring hospitalization (e.g., heart disease).[11]

Pharmacotherapy is the cornerstone of hospital treatment, and it is well‐known that it affects multiple physiologic systems causing side effects apart from the condition they are approved to treat. Given that geriatric syndromes are a result of impairments in multiple organ systems, it is plausible that pharmacotherapy may initiate or worsen these syndromes.[12] Medication‐related problems in older adults are well known. Polypharmacy and adverse drug events (as a result of drug‐drug/disease interactions and changes in pharmacokinetics and pharmacodynamics) are prevalent in multimorbid elderly patients.[13, 14, 15, 16] The prescribing cascade[17] increases the medication burden and may be a contributing factor for geriatric syndromes in hospitalized patients.[18] For instance, laxatives may be prescribed to counteract constipation caused by anticholinergic drugs.

The American Geriatric Society (AGS) Beers list[19, 20] and similar criteria[21] provide excellent resources to identify medications with potentially harmful interactions or adverse effects in older adults. Although these lists include medicines associated with a specific geriatric syndrome, they were not developed to explicitly link medicines across multiple geriatric syndromes, regardless of indication or appropriateness. For example, medications that effect important geriatric syndromes like unintentional weight/appetite loss, depression, and urinary incontinence are not extensively covered. In addition, disease‐appropriate medications (eg, ‐blockers for systolic heart failure), that may be associated with a geriatric syndrome (eg, falls) are not included; however, they may be important to consider for a patient and clinician who are weighing the disease benefits compared to the geriatric syndrome‐related risks. Finally, the AGS 2015 Beers criteria panel mentions the limitation that many medication associations may be excluded because older adults are less represented in clinical trials.[20] Clinicians are currently limited in identifying medications potentially contributing to a broad set of geriatric syndromes in their patients without a specific list of medications associated with geriatric syndromes (MAGS).[20]

In response to this gap, identifying these medications is important and should be a starting point in efforts toward prevention and treatment of geriatric syndromes. The 2 main objectives of this study were to first identify medications that may meaningfully contribute to 6 geriatric syndromes and subsequently describe the frequency of these medications in a population transitioning from acute care to postacute care to highlight the need and potential impact of such a list.

METHODS

This study included 2 phases that aligned with our 2 primary objectives. Phase 1 involved identifying medications associated with 6 geriatric syndromes, and phase 2 included a cross‐sectional analysis of the prevalence of these medications in a sample of patients discharged to SNFs.

Phase 1: Development of the MAGS List

Figure 1 depicts the underlying conceptual model and approach that was used in phase 1. The interaction between the patient factors and medication leads to polypharmacy that contributes to geriatric syndromes and additional adverse outcomes. As a starting point for mitigating geriatric syndromes, we used an iterative analytical process to identify a list of medications associated with the following geriatric syndromes that were documented to be highly prevalent in patients discharged to SNFs: cognitive impairment, delirium, falls, unintentional weight and/or appetite loss, urinary incontinence, and depression.[8] To be inclusive and sensitive, our approach differed from traditional systematic reviews, and in fact was meant to bring together much of the established systematic literature about disparate geriatric syndromes in 1 place, because patients often do not experience a geriatric syndrome in isolation, but rather experience multiple geriatric syndromes.[8] The MAGS list had 3 main inclusion criteria (Figure 1): (1) evidence in the published literature (systematic reviews, cohort studies, randomized clinical trials) that the medication is related to the syndrome, (2) expert panel opinion, and (3) drug databases (Lexicomp Online database[22] and/or US Food and Drug Administration [FDA]approved package inserts).[23] We generated an initial list of medications based on these 3 main criteria to identify medications with significant associations to each geriatric syndrome. The list was further expanded and vetted using an iterative review of each medication list as it related to each geriatric syndrome through a series of group meetings focused around each geriatric syndrome. Following further discussion, we obtained agreement among all team members for medications included in the final list. For each geriatric syndrome, we excluded medications from consideration if they were used to treat the same geriatric syndrome (eg, ‐adrenergic blockers used to treat incontinence in men were listed as associated with incontinence only in women). We classified medications according to the Established Pharmacologic Class available at the FDA website. We also compared our final MAGS list with the 2015 AGS Beer's list[20] by identifying medications that were related to the 6 geriatric syndromes. This included Beers[20]‐cited rationale of anticholinergic, extrapyramidal symptoms, orthostatic hypotension (eg, falls), high‐risk adverse central nervous system effects, sedating, cognitive decline (eg, antipsychotics), delirium, falls, fractures, incontinence, and gastrointestinal (eg, nausea, vomiting). Specifically, we assessed whether the medications were included as inappropriate by the AGS Beers 2015[20] list and also whether they documented the syndrome association for that medication.

Figure 1
Conceptual model and approach for development of the medication associated with geriatric syndromes (MAGS) list (phase 1).

Phase 2: Prevalence of MAGS in Hospitalized Older Adults Discharged to SNFs

Sample

We next applied the MAGS list to a convenience sample of hospitalized patients discharged to SNFs to assess the prevalence of MAGS in this sample, and also to compare with the prevalence of Beers criteria[20] medications. Our sample was selected from data collected as part of a quality‐improvement project to reduce hospital readmissions in patients discharged to SNFs. The larger study enrolled a total 1093 medical and surgical patients who had Medicare insurance eligibility and were discharged from 1 large university hospital to 23 area SNFs from January 17, 2013 through July 31, 2014. The university institutional review board waived the requirement for written consent. For the purpose of this substudy. we selected the first 154 patients with complete chart abstraction (approximately 15% of the total) as a convenience sample.

Data Analysis

We applied descriptive statistics to summarize demographic and clinical characteristics of the convenience sample. To understand potential selection biases that could have resulted by the convenience sampling, we compared participant characteristics of the convenience sample (N = 154) with the characteristics of the remaining participants of the larger study (N = 939) using independent sample t tests and 2 tests for continuous and categorical measures, respectively. We applied the MAGS list and the AGS 2015 Beers criteria[20] for the sample of 154 and identified the medications associated with each of the 6 geriatric syndromes from the discharge medication lists completed by hospital clinical pharmacists. For each patient, we identified both scheduled and PRN (pro re nata, or as needed) medications associated with each geriatric syndrome. Thereafter, we determined whether the discharge list contained at least 1 medication associated with a geriatric syndrome per the MAGS list and the AGS Beers 2015 criteria,[20] and the percentage of overall medications that were part of the MAGS and Beers lists. Data were aggregated using means and standard deviations across syndromes (ie, number of discharge medications per syndrome per patient) along with the percentage of patients with 1 or more medications related to a specific syndrome and the percentage of medications that were MAGS. All analyses were performed using the SPSS statistical package (IBM SPSS Statistics for Windows, version 23.0; IBM, Armonk, NY).

RESULTS

Phase 1: MAGS List

The iterative process applied in this analysis generated a list of 513 medications associated with the 6 geriatric syndromes. The list of medications related to each syndrome and the corresponding rationale and relevant references for their inclusion is presented in the Supporting Information, Appendix 1, in the online version of this article. Table 1 summarizes these medications across 18 major drug categories. Antiepileptics were linked to all 6 geriatric syndromes, whereas antipsychotics, antidepressants, antiparkinsonism, and opioid agonists were associated with 5 syndromes. Ten of the 18 categories were associated with 3 geriatric syndromescognitive impairment, delirium, and falls. Four medication categories were associated with only 1 syndrome. Nonopioid/nonsteroidal anti‐inflammatory and/or analgesics and nonopioid cough suppressant and expectorant medications were associated with falls syndrome only. Hormone replacement medications were associated with depression only, and immunosuppressants were associated with unintentional weight and appetite loss only.

Summary of Medications Associated With Geriatric Syndromes
Major Medication Category Delirium Cognitive Impairment Falls Unintentional Weight and Appetite Loss Urinary Incontinence Depression Drug Class/Drug Within Each Category
  • NOTE: Associated syndrome checked if at least 2 or more medications within the wider class are associated with the syndrome. Abbreviations: NSAIDs, nonsteroidal anti‐inflammatory drugs.

Antipsychotics Atypical and typical antipsychotics, buspirone
Antidepressants Tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitor, aminoketone
Antiepileptics Antiepileptics, mood stabilizers, barbiturates
Antiparkinsonism Aromatic amino acid decarboxylation inhibitor and catechol‐o‐methyltransferase inhibitor, catecholamine‐depleting sympatholytic, catechol‐o‐methyltransferase inhibitor, dopaminergic agonist, ergot derivative, monoamine oxidase inhibitor, nonergot dopamine agonist,
Benzodiazapines Benzodiazapines only
Nonbenzodiazepine hypnotics Benzodiazepine analogs, nonbenzodiazepine hypnotics, tranquilizers, ‐aminobutyric acid A receptor agonist
Opioid agonists Full or partial opioid agonists, opiates, opioids
Nonopioid/nonsteroidal anti‐inflammatory and/or analgesics Nonopioid analgesics, NSAIDs, COX‐2 selective inhibitor NSAIDs
Antihypertensives Calcium channel blocker, ‐adrenergic blocker, angiotensin‐converting enzyme inhibitor, angiotensin 2 receptor blocker, ‐adrenergic blocker, diuretics (loop, potassium sparing, thiazide), nitrate vasodilators, aldosterone blocker
Antiarrhythmic Antiarrhythmics, cardiac glycosides
Antidiabetics Insulin and insulin analogs, sulfonylureas, ‐glucosidase inhibitor, amylin analog, biguanide, glinide, GLP‐1 receptor agonist, glucagon‐like peptide‐1 agonist
Anticholinergics and/or antihistaminics Anticholinergics, histamine receptor antagonists, muscarininc antagonists, combined anticholinergics, and histamine receptor antagonists
Antiemetics Antiemetics, dopaminergic antagonists, dopamine‐2 receptor antagonist
Hormone replacement Corticosteroids, progestin, estrogen, estrogen agonist/antagonist, gonadotropin releasing hormone receptor agonist
Muscle relaxers Muscle relaxers
Immunosuppressants Calcineurin inhibitor immunosuppressant, folate analog metabolic inhibitor, purine antimetabolite
Nonopioid cough suppressants and expectorants Expectorant, non‐narcotic antitussive, ‐1 agonist, uncompetitive N‐methyl‐D‐aspartate receptor antagonist
Antimicrobials Macrolide, cephalosporin, penicillin class, rifamycin, non‐nucleoside analog reverse transcriptase inhibitor, influenza A M2 protein inhibitor
Others ‐3‐adrenergic agonist, methylxanthine, cholinesterase inhibitor, interferon and , partial cholinergic nicotinic agonist, tyrosine hydroxylase, retinoid, serotonin‐1b and serotonin‐1d receptor agonist, stimulant laxative, vitamin K antagonist, platelet aggregation inhibitor

Approximately 58% of the medications overlapped with the AGS 2015 Beer's Criteria[20] irrespective of whether the specific syndrome association was stated in the rationale.[20] Medications that overlapped were mostly in the delirium, cognitive impairment, and falls category with only a few overlaps in depression, unintentional weight loss, and urinary incontinence lists (see Supporting Information, Appendix 1, in the online version of this article).

Phase 2: Prevalence of MAGS

Among 154 participants, the mean age was 76.5 (10.6) years, 64.3% were female, 77.9% were white, and 96.1% non‐Hispanic. The median hospital length of stay was 6 days, with an interquartile range of 5 days. The orthopedic service discharged the highest proportion of patients (24%), followed by the geriatrics and internal medicine services, which each discharged 19.5% of the patients (Table 2). The remaining participants of the larger quality‐improvement project (N = 939) did not significantly differ on these demographic and clinical characteristics except for hospital length of stay, which was shorter in the sample analyzed (see Supporting Information, Appendix 2, in the online version of this article).

Baseline Characteristics for a Sample of 154 Medicare InsuranceEligible Patients Discharged to Skilled Nursing Facilities (N = 154)
Baseline Characteristics Mean ( SD) or Percent (n)
  • NOTE: Abbreviations: IQR, interquartile range; SD, standard deviation.

Age, y 76.5 ( 10.6)
Sex
Female 64.3% (99)
Race
White 77.9% (126)
Black 16.2% (25)
Unknown 0.6% (1)
Declined 0.6% (1)
Missing 0.6% (1)
Ethnicity
Non‐Hispanic 96.1% (148)
Hispanic 1.3% (2)
Unknown 2.6% (4)
Hospital length of stay, d 7.0 ( 4.2)
Hospital length of stay, d, median (IQR) 6.0 (5.0)
No. of hospital discharge medications, count 14.0 ( 4.7)
Discharge service
Orthopedic service 24.0% (37)
Geriatric service 19.5% (30)
Internal medicine 19.5% (30)
Other 37.0% (57)

Patients were discharged to SNFs with an average of 14.0 (4.7) medication orders. Overall, 43% (13%) of these discharge medication orders were MAGS. Every patient in the sample was ordered at least 1 medication associated with geriatric syndromes. Multiple MAGS were the norm, with an average of 5.9 (2.2) MAGS per patient. MAGS were also the norm, as 98.1% of the sample had medication orders associated with at least 2 different syndromes.

When the Beer's criteria[20] were applied to the medication orders (instead of the MAGS list), problematic medications appeared less common. Patients had an average of 3.04 (1.7) MAGS that were also listed on the AGS 2015 Beer's list,[20] representing an average of 22.3% of all discharge orders.

Table 3 illustrates the average number of medications per patient associated with each syndrome, and the percentage of patients (number in parentheses) discharged with at least 1 medication associated with each syndrome per the MAGS list and the Beers 2015 criteria.[20] For example, per the MAGS list, the syndrome most frequently associated with medications was falls, with patients discharged on an average of 5.5 (2.2) medications associated with falls, and 100% of the sample had at least 1 discharge medication associated with falls. Alternatively, the syndrome associated with the lowest frequency of medications was unintentional weight loss (with an average of 0.38 medications per patient), although 36% of these patients had more than 1 discharge medication associated with weight loss. As seen in Table 3, the mean and prevalence of 1 or more medications associated with each of the geriatric syndromes as identified by the Beers 2015 criteria[20] was lower than those identified by the MAGS list developed for this study.

Prevalence of Medications Associated With Geriatric Syndromes per MAGS and AGS Beers 2015 Criteria in an Older Cohort of Hospitalized Patients Discharged to Skilled Nursing Facilities (N = 154)
Geriatric Syndromes Associated Medications per MAGS List Associated Medications per AGS Beers 2015 Criteria
Mean SD Percentage of Patients Receiving 1 Related Medication Mean SD Percentage of Patients Receiving 1 Related Medication
  • NOTE: Abbreviations: AGS, American Geriatric Society; MAGS, Medications Associated With Geriatric Syndromes, SD, standard deviation.

Cognitive impairment 1.8 ( 1.2) 84.4% (130) 1.6 ( 1.2) 78.6% (121)
Delirium 1.4 ( 1.1) 76.0% (117) 1.3 ( 1.2) 68.2% (105)
Falls 5.5 ( 2.2) 100% (154) 2.6 ( 1.6) 92.2% (142)
Unintentional weight and/or appetite loss 0.4 ( 0.5) 36.3% (56) 0.1 ( 0.3) 6.5% (10)
Urinary incontinence 1.6 ( 1.0) 85.7% (132) 0.1 ( 0.2) 5.8% (9)
Depression 1.7 ( 1.0) 90.9% (140) 0.0 ( 0.0) 0.0% (0)
All syndromes 5.9 ( 2.2) 100% (154) 3.0 ( 1.7) 95% (149)

DISCUSSION

An iterative process of evidence review by a multidisciplinary panel resulted in a list of 513 medications associated with 6 common geriatric syndromes. This analysis demonstrated that hospitalized, older patients discharged to SNFs were frequently prescribed MAGS. The rate of prescribing ranged from 100% of patients with a medication associated with falls to 36% for unintentional weight loss. Moreover, an alarming 43% of all medications at hospital discharge were MAGS. For this vulnerable population, the combination of high prevalence of MAGS and high risk of geriatric syndromes emphasize a need to critically review the risks and benefits of MAGS throughout hospitalization and at the time of discharge.

A body of evidence demonstrates that many drugs in a typical older adult regimen have no specific clinical indication, are considered inappropriate, or have uncertain efficacy in the geriatric population.[24, 25, 26] This study builds on the foundational work described in landmark reviews such as the AGS Beers[20] and STOPP/START[21] (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions/Screening Tool to Alert doctors to Right, i.e. appropriate indicated Treatment) criteria. Both of these tools, however, were specifically designed as screening tools to identify medications considered unsafe for older adults under most circumstances and within specific illness states.[19, 20, 21] They are most often utilized when starting a medication to avoid acute adverse events. In contrast, the MAGS list was developed to be inclusive of medications that are often appropriate for many medical diagnoses but may also contribute to underlying geriatric syndromes that are more chronic in nature. In addition, inclusion of such medicines increases the sensitivity of screening for medications that can be targeted through patient‐centered deprescribing efforts when clinically appropriate.

A major strength of this study is that we bring together evidence across a spectrum of geriatric syndromes commonly experienced by hospitalized elders. In addition to evaluating multiple syndromes, we applied multiple modalities; particularly the use of an iterative review process by a multidisciplinary team of experts and using Lexicomp and FDA insert packages for linking medications to specific geriatric conditions. The inclusion criteria were broadened beyond single sources of evidence in an effort to capture a comprehensive list of medications. As a result, the MAGS list can be implemented as a screening tool for deprescribing interventions and assessing medication appropriateness to address individual or clusters of geriatric syndromes within a patient.

In addition to expanding this knowledge base, clinical relevance of the MAGS list is highlighted by its application to a sample of hospitalized older adults discharged to SNFs, a cohort known to experience geriatric syndromes. In fact, 43% of patients' medications at hospital discharge were MAGS. Importantly, due to the cross‐sectional nature of this study, we cannot be certain if the medication caused or potentiated each of the geriatric syndromes. However, hospitals and SNFs are devoting major resources toward reduction of falls, avoidance of urinary catheter use, and reduction of preventable readmissions. These efforts can be complemented by considering the number of medications associated with falls, urinary incontinence, and overall MAGS burden. The striking prevalence of MAGS demonstrates a rigorous need to weigh the risks and benefits of these medications. Above all, the intent of this study is not to propose that any MAGS be reflexively stopped, but rather that the MAGS list should facilitate a holistic approach to care for the complex older adult. For example, standard therapies such as gabapentin may be appropriate for treating neuralgic pain but may also contribute to falls and urinary incontinence. Thus, alternative pain treatments could be selected in place of gabapentin for a 75‐year old patient who is experiencing recurrent falls and increasing incontinence. Therefore, the MAGS list enables a patient‐provider discussion wherein medications' therapeutic benefits can be weighed against risks posed by specific clusters of geriatric syndromes, potential impact on quality of life, and consistency with goals of care.

This study has some limitations. First, although we examined a broad number of geriatric syndromes, several other geriatric syndromes experienced by hospitalized older adults were not addressed including: fecal incontinence, insomnia, and functional impairment. These syndromes were intentionally excluded from the study a priori due to reasons of feasibility and scope. Second, unlike the Beer's 2015 criteria, the MAGS list does not sub‐classify associations of medications with geriatric syndromes for patients with specific diseases (eg, heart failure). In fact, our MAGS list included medications often indicated in treating these diagnoses. A clinician must work with the patient to weigh the disease‐specific benefits of some medications with the potential effect on geriatric syndrome symptoms and outcomes. Third, the instrument has a very high sensitivity, which was intended to generate an inclusive list of medications that enables providers to weigh risks of geriatric syndromes with the intended indication benefit. The objective is not to use this list as a reflexive tool but rather help clinicians identify a starting point to address geriatric syndromes in their patients to make patient‐centered medication decisions. Although the MAGS list is intentionally large (sensitive), the advent of advanced bioinformatics can enable MAGS to be assessed in the future for both clinical and research purposes. Fourth, FDA insert packages and Lexicomp databases report anything experienced by the patient while on the particular medication, but it might not necessarily imply a causative link. The high use of MAGS and the specific geriatric syndrome may coexist due to the high prevalence and interplay of multimorbidity, polypharmacy, and geriatric syndromes in this population. Last, the list was developed by expert panel members predominantly from a single institution, which may introduce bias. Despite these limitations, the prevalence of these medications in a sample of patients transitioning from acute to postacute care highlights the utility of the MAGS list in future clinical research and quality improvement endeavors.

In conclusion, the MAGS list provides a comprehensive and sensitive indicator of medications associated with any of 6 geriatric syndromes regardless of medication indication and appropriateness. The MAGS list provides an overall degree of medication burden with respect to geriatric syndromes and a foundation for future research to assess the relationship between the presence of geriatric syndromes and syndrome‐associated medications. The MAGS list is an important first step in summarizing the data that link medications to geriatric syndromes. Future studies are needed to broaden the analysis of MAGS for other common geriatric syndromes and to identify new and emerging medications not present during the time of this analysis. The MAGS list has the potential to facilitate deprescribing efforts needed to combat the epidemic of overprescribing that may be contributing to the burden of geriatric syndromes among older patients.

Acknowledgements

The authors thank Dr. Linda Beuscher, Dr. Patricia Blair Miller, Dr. Joseph Ouslander, Dr. William Stuart Reynolds, and Dr. Warren Taylor for providing their expertise and participating in the expert panel discussions that facilitated the development of the MAGS list. The authors also recognize the research support provided by Christopher Simon Coelho.

Disclosures: This research was supported by the Department of Health and Human Services, Centers for Medicare & Medicaid Services grant #1C1CMS331006 awarded to Principal Investigator, John F. Schnelle, PhD. Dr. Vasilevskis was supported by the National Institute on Aging of the National Institutes of Health award K23AG040157 and the Geriatric Research, Education and Clinical Center. Dr. Bell was supported by National Institute on Aging‐K award K23AG048347‐01A1. Dr. Mixon is supported by a Veterans Affairs Health Services Research & Development Career Development Award (12‐168). This research was also supported by the National Center for Advancing Translational Sciences Clinical and Translational Science award UL1TR000445. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the US Department of Health and Human Services or any of its agencies, the National Center for Advancing Translation Science, the National Institutes of Health, or the Department of Veterans Affairs. Each coauthor contributed significantly to the manuscript. Dr. Kripalani has received stock/stock options from Bioscape Digital, LLC. None of the other authors have significant conflicts of interest to report related to this project or the results reported within this article.

Geriatric syndromes are common clinical conditions in older adults that do not fall into specific disease categories. Unlike the traditional definition of a syndrome, geriatric syndrome refers to a condition that is mediated by multiple shared underlying risk factors.[1, 2] Conditions commonly referred to as geriatric syndromes include delirium, cognitive impairment, falls, unintentional weight loss, depressive symptoms, and incontinence. Even though many perceive it as medical misnomer,[3] geriatric syndromes have been shown to negatively impact quality of life and activities of daily living in older adults.[2] They are also associated with adverse outcomes such as increased healthcare utilization, functional decline, and mortality, even after adjusting for age and disease severity.[4, 5, 6] Hospitalized older adults, including those discharged to skilled nursing facilities (SNFs)[7, 8] are particularly at high risk for new‐onset or exacerbation of geriatric syndromes and poor outcomes.[7, 9, 10] However, hospital providers seldom assess, manage, or document geriatric syndromes because they are often overshadowed by disease conditions that lead to an acute episode requiring hospitalization (e.g., heart disease).[11]

Pharmacotherapy is the cornerstone of hospital treatment, and it is well‐known that it affects multiple physiologic systems causing side effects apart from the condition they are approved to treat. Given that geriatric syndromes are a result of impairments in multiple organ systems, it is plausible that pharmacotherapy may initiate or worsen these syndromes.[12] Medication‐related problems in older adults are well known. Polypharmacy and adverse drug events (as a result of drug‐drug/disease interactions and changes in pharmacokinetics and pharmacodynamics) are prevalent in multimorbid elderly patients.[13, 14, 15, 16] The prescribing cascade[17] increases the medication burden and may be a contributing factor for geriatric syndromes in hospitalized patients.[18] For instance, laxatives may be prescribed to counteract constipation caused by anticholinergic drugs.

The American Geriatric Society (AGS) Beers list[19, 20] and similar criteria[21] provide excellent resources to identify medications with potentially harmful interactions or adverse effects in older adults. Although these lists include medicines associated with a specific geriatric syndrome, they were not developed to explicitly link medicines across multiple geriatric syndromes, regardless of indication or appropriateness. For example, medications that effect important geriatric syndromes like unintentional weight/appetite loss, depression, and urinary incontinence are not extensively covered. In addition, disease‐appropriate medications (eg, ‐blockers for systolic heart failure), that may be associated with a geriatric syndrome (eg, falls) are not included; however, they may be important to consider for a patient and clinician who are weighing the disease benefits compared to the geriatric syndrome‐related risks. Finally, the AGS 2015 Beers criteria panel mentions the limitation that many medication associations may be excluded because older adults are less represented in clinical trials.[20] Clinicians are currently limited in identifying medications potentially contributing to a broad set of geriatric syndromes in their patients without a specific list of medications associated with geriatric syndromes (MAGS).[20]

In response to this gap, identifying these medications is important and should be a starting point in efforts toward prevention and treatment of geriatric syndromes. The 2 main objectives of this study were to first identify medications that may meaningfully contribute to 6 geriatric syndromes and subsequently describe the frequency of these medications in a population transitioning from acute care to postacute care to highlight the need and potential impact of such a list.

METHODS

This study included 2 phases that aligned with our 2 primary objectives. Phase 1 involved identifying medications associated with 6 geriatric syndromes, and phase 2 included a cross‐sectional analysis of the prevalence of these medications in a sample of patients discharged to SNFs.

Phase 1: Development of the MAGS List

Figure 1 depicts the underlying conceptual model and approach that was used in phase 1. The interaction between the patient factors and medication leads to polypharmacy that contributes to geriatric syndromes and additional adverse outcomes. As a starting point for mitigating geriatric syndromes, we used an iterative analytical process to identify a list of medications associated with the following geriatric syndromes that were documented to be highly prevalent in patients discharged to SNFs: cognitive impairment, delirium, falls, unintentional weight and/or appetite loss, urinary incontinence, and depression.[8] To be inclusive and sensitive, our approach differed from traditional systematic reviews, and in fact was meant to bring together much of the established systematic literature about disparate geriatric syndromes in 1 place, because patients often do not experience a geriatric syndrome in isolation, but rather experience multiple geriatric syndromes.[8] The MAGS list had 3 main inclusion criteria (Figure 1): (1) evidence in the published literature (systematic reviews, cohort studies, randomized clinical trials) that the medication is related to the syndrome, (2) expert panel opinion, and (3) drug databases (Lexicomp Online database[22] and/or US Food and Drug Administration [FDA]approved package inserts).[23] We generated an initial list of medications based on these 3 main criteria to identify medications with significant associations to each geriatric syndrome. The list was further expanded and vetted using an iterative review of each medication list as it related to each geriatric syndrome through a series of group meetings focused around each geriatric syndrome. Following further discussion, we obtained agreement among all team members for medications included in the final list. For each geriatric syndrome, we excluded medications from consideration if they were used to treat the same geriatric syndrome (eg, ‐adrenergic blockers used to treat incontinence in men were listed as associated with incontinence only in women). We classified medications according to the Established Pharmacologic Class available at the FDA website. We also compared our final MAGS list with the 2015 AGS Beer's list[20] by identifying medications that were related to the 6 geriatric syndromes. This included Beers[20]‐cited rationale of anticholinergic, extrapyramidal symptoms, orthostatic hypotension (eg, falls), high‐risk adverse central nervous system effects, sedating, cognitive decline (eg, antipsychotics), delirium, falls, fractures, incontinence, and gastrointestinal (eg, nausea, vomiting). Specifically, we assessed whether the medications were included as inappropriate by the AGS Beers 2015[20] list and also whether they documented the syndrome association for that medication.

Figure 1
Conceptual model and approach for development of the medication associated with geriatric syndromes (MAGS) list (phase 1).

Phase 2: Prevalence of MAGS in Hospitalized Older Adults Discharged to SNFs

Sample

We next applied the MAGS list to a convenience sample of hospitalized patients discharged to SNFs to assess the prevalence of MAGS in this sample, and also to compare with the prevalence of Beers criteria[20] medications. Our sample was selected from data collected as part of a quality‐improvement project to reduce hospital readmissions in patients discharged to SNFs. The larger study enrolled a total 1093 medical and surgical patients who had Medicare insurance eligibility and were discharged from 1 large university hospital to 23 area SNFs from January 17, 2013 through July 31, 2014. The university institutional review board waived the requirement for written consent. For the purpose of this substudy. we selected the first 154 patients with complete chart abstraction (approximately 15% of the total) as a convenience sample.

Data Analysis

We applied descriptive statistics to summarize demographic and clinical characteristics of the convenience sample. To understand potential selection biases that could have resulted by the convenience sampling, we compared participant characteristics of the convenience sample (N = 154) with the characteristics of the remaining participants of the larger study (N = 939) using independent sample t tests and 2 tests for continuous and categorical measures, respectively. We applied the MAGS list and the AGS 2015 Beers criteria[20] for the sample of 154 and identified the medications associated with each of the 6 geriatric syndromes from the discharge medication lists completed by hospital clinical pharmacists. For each patient, we identified both scheduled and PRN (pro re nata, or as needed) medications associated with each geriatric syndrome. Thereafter, we determined whether the discharge list contained at least 1 medication associated with a geriatric syndrome per the MAGS list and the AGS Beers 2015 criteria,[20] and the percentage of overall medications that were part of the MAGS and Beers lists. Data were aggregated using means and standard deviations across syndromes (ie, number of discharge medications per syndrome per patient) along with the percentage of patients with 1 or more medications related to a specific syndrome and the percentage of medications that were MAGS. All analyses were performed using the SPSS statistical package (IBM SPSS Statistics for Windows, version 23.0; IBM, Armonk, NY).

RESULTS

Phase 1: MAGS List

The iterative process applied in this analysis generated a list of 513 medications associated with the 6 geriatric syndromes. The list of medications related to each syndrome and the corresponding rationale and relevant references for their inclusion is presented in the Supporting Information, Appendix 1, in the online version of this article. Table 1 summarizes these medications across 18 major drug categories. Antiepileptics were linked to all 6 geriatric syndromes, whereas antipsychotics, antidepressants, antiparkinsonism, and opioid agonists were associated with 5 syndromes. Ten of the 18 categories were associated with 3 geriatric syndromescognitive impairment, delirium, and falls. Four medication categories were associated with only 1 syndrome. Nonopioid/nonsteroidal anti‐inflammatory and/or analgesics and nonopioid cough suppressant and expectorant medications were associated with falls syndrome only. Hormone replacement medications were associated with depression only, and immunosuppressants were associated with unintentional weight and appetite loss only.

Summary of Medications Associated With Geriatric Syndromes
Major Medication Category Delirium Cognitive Impairment Falls Unintentional Weight and Appetite Loss Urinary Incontinence Depression Drug Class/Drug Within Each Category
  • NOTE: Associated syndrome checked if at least 2 or more medications within the wider class are associated with the syndrome. Abbreviations: NSAIDs, nonsteroidal anti‐inflammatory drugs.

Antipsychotics Atypical and typical antipsychotics, buspirone
Antidepressants Tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitor, aminoketone
Antiepileptics Antiepileptics, mood stabilizers, barbiturates
Antiparkinsonism Aromatic amino acid decarboxylation inhibitor and catechol‐o‐methyltransferase inhibitor, catecholamine‐depleting sympatholytic, catechol‐o‐methyltransferase inhibitor, dopaminergic agonist, ergot derivative, monoamine oxidase inhibitor, nonergot dopamine agonist,
Benzodiazapines Benzodiazapines only
Nonbenzodiazepine hypnotics Benzodiazepine analogs, nonbenzodiazepine hypnotics, tranquilizers, ‐aminobutyric acid A receptor agonist
Opioid agonists Full or partial opioid agonists, opiates, opioids
Nonopioid/nonsteroidal anti‐inflammatory and/or analgesics Nonopioid analgesics, NSAIDs, COX‐2 selective inhibitor NSAIDs
Antihypertensives Calcium channel blocker, ‐adrenergic blocker, angiotensin‐converting enzyme inhibitor, angiotensin 2 receptor blocker, ‐adrenergic blocker, diuretics (loop, potassium sparing, thiazide), nitrate vasodilators, aldosterone blocker
Antiarrhythmic Antiarrhythmics, cardiac glycosides
Antidiabetics Insulin and insulin analogs, sulfonylureas, ‐glucosidase inhibitor, amylin analog, biguanide, glinide, GLP‐1 receptor agonist, glucagon‐like peptide‐1 agonist
Anticholinergics and/or antihistaminics Anticholinergics, histamine receptor antagonists, muscarininc antagonists, combined anticholinergics, and histamine receptor antagonists
Antiemetics Antiemetics, dopaminergic antagonists, dopamine‐2 receptor antagonist
Hormone replacement Corticosteroids, progestin, estrogen, estrogen agonist/antagonist, gonadotropin releasing hormone receptor agonist
Muscle relaxers Muscle relaxers
Immunosuppressants Calcineurin inhibitor immunosuppressant, folate analog metabolic inhibitor, purine antimetabolite
Nonopioid cough suppressants and expectorants Expectorant, non‐narcotic antitussive, ‐1 agonist, uncompetitive N‐methyl‐D‐aspartate receptor antagonist
Antimicrobials Macrolide, cephalosporin, penicillin class, rifamycin, non‐nucleoside analog reverse transcriptase inhibitor, influenza A M2 protein inhibitor
Others ‐3‐adrenergic agonist, methylxanthine, cholinesterase inhibitor, interferon and , partial cholinergic nicotinic agonist, tyrosine hydroxylase, retinoid, serotonin‐1b and serotonin‐1d receptor agonist, stimulant laxative, vitamin K antagonist, platelet aggregation inhibitor

Approximately 58% of the medications overlapped with the AGS 2015 Beer's Criteria[20] irrespective of whether the specific syndrome association was stated in the rationale.[20] Medications that overlapped were mostly in the delirium, cognitive impairment, and falls category with only a few overlaps in depression, unintentional weight loss, and urinary incontinence lists (see Supporting Information, Appendix 1, in the online version of this article).

Phase 2: Prevalence of MAGS

Among 154 participants, the mean age was 76.5 (10.6) years, 64.3% were female, 77.9% were white, and 96.1% non‐Hispanic. The median hospital length of stay was 6 days, with an interquartile range of 5 days. The orthopedic service discharged the highest proportion of patients (24%), followed by the geriatrics and internal medicine services, which each discharged 19.5% of the patients (Table 2). The remaining participants of the larger quality‐improvement project (N = 939) did not significantly differ on these demographic and clinical characteristics except for hospital length of stay, which was shorter in the sample analyzed (see Supporting Information, Appendix 2, in the online version of this article).

Baseline Characteristics for a Sample of 154 Medicare InsuranceEligible Patients Discharged to Skilled Nursing Facilities (N = 154)
Baseline Characteristics Mean ( SD) or Percent (n)
  • NOTE: Abbreviations: IQR, interquartile range; SD, standard deviation.

Age, y 76.5 ( 10.6)
Sex
Female 64.3% (99)
Race
White 77.9% (126)
Black 16.2% (25)
Unknown 0.6% (1)
Declined 0.6% (1)
Missing 0.6% (1)
Ethnicity
Non‐Hispanic 96.1% (148)
Hispanic 1.3% (2)
Unknown 2.6% (4)
Hospital length of stay, d 7.0 ( 4.2)
Hospital length of stay, d, median (IQR) 6.0 (5.0)
No. of hospital discharge medications, count 14.0 ( 4.7)
Discharge service
Orthopedic service 24.0% (37)
Geriatric service 19.5% (30)
Internal medicine 19.5% (30)
Other 37.0% (57)

Patients were discharged to SNFs with an average of 14.0 (4.7) medication orders. Overall, 43% (13%) of these discharge medication orders were MAGS. Every patient in the sample was ordered at least 1 medication associated with geriatric syndromes. Multiple MAGS were the norm, with an average of 5.9 (2.2) MAGS per patient. MAGS were also the norm, as 98.1% of the sample had medication orders associated with at least 2 different syndromes.

When the Beer's criteria[20] were applied to the medication orders (instead of the MAGS list), problematic medications appeared less common. Patients had an average of 3.04 (1.7) MAGS that were also listed on the AGS 2015 Beer's list,[20] representing an average of 22.3% of all discharge orders.

Table 3 illustrates the average number of medications per patient associated with each syndrome, and the percentage of patients (number in parentheses) discharged with at least 1 medication associated with each syndrome per the MAGS list and the Beers 2015 criteria.[20] For example, per the MAGS list, the syndrome most frequently associated with medications was falls, with patients discharged on an average of 5.5 (2.2) medications associated with falls, and 100% of the sample had at least 1 discharge medication associated with falls. Alternatively, the syndrome associated with the lowest frequency of medications was unintentional weight loss (with an average of 0.38 medications per patient), although 36% of these patients had more than 1 discharge medication associated with weight loss. As seen in Table 3, the mean and prevalence of 1 or more medications associated with each of the geriatric syndromes as identified by the Beers 2015 criteria[20] was lower than those identified by the MAGS list developed for this study.

Prevalence of Medications Associated With Geriatric Syndromes per MAGS and AGS Beers 2015 Criteria in an Older Cohort of Hospitalized Patients Discharged to Skilled Nursing Facilities (N = 154)
Geriatric Syndromes Associated Medications per MAGS List Associated Medications per AGS Beers 2015 Criteria
Mean SD Percentage of Patients Receiving 1 Related Medication Mean SD Percentage of Patients Receiving 1 Related Medication
  • NOTE: Abbreviations: AGS, American Geriatric Society; MAGS, Medications Associated With Geriatric Syndromes, SD, standard deviation.

Cognitive impairment 1.8 ( 1.2) 84.4% (130) 1.6 ( 1.2) 78.6% (121)
Delirium 1.4 ( 1.1) 76.0% (117) 1.3 ( 1.2) 68.2% (105)
Falls 5.5 ( 2.2) 100% (154) 2.6 ( 1.6) 92.2% (142)
Unintentional weight and/or appetite loss 0.4 ( 0.5) 36.3% (56) 0.1 ( 0.3) 6.5% (10)
Urinary incontinence 1.6 ( 1.0) 85.7% (132) 0.1 ( 0.2) 5.8% (9)
Depression 1.7 ( 1.0) 90.9% (140) 0.0 ( 0.0) 0.0% (0)
All syndromes 5.9 ( 2.2) 100% (154) 3.0 ( 1.7) 95% (149)

DISCUSSION

An iterative process of evidence review by a multidisciplinary panel resulted in a list of 513 medications associated with 6 common geriatric syndromes. This analysis demonstrated that hospitalized, older patients discharged to SNFs were frequently prescribed MAGS. The rate of prescribing ranged from 100% of patients with a medication associated with falls to 36% for unintentional weight loss. Moreover, an alarming 43% of all medications at hospital discharge were MAGS. For this vulnerable population, the combination of high prevalence of MAGS and high risk of geriatric syndromes emphasize a need to critically review the risks and benefits of MAGS throughout hospitalization and at the time of discharge.

A body of evidence demonstrates that many drugs in a typical older adult regimen have no specific clinical indication, are considered inappropriate, or have uncertain efficacy in the geriatric population.[24, 25, 26] This study builds on the foundational work described in landmark reviews such as the AGS Beers[20] and STOPP/START[21] (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions/Screening Tool to Alert doctors to Right, i.e. appropriate indicated Treatment) criteria. Both of these tools, however, were specifically designed as screening tools to identify medications considered unsafe for older adults under most circumstances and within specific illness states.[19, 20, 21] They are most often utilized when starting a medication to avoid acute adverse events. In contrast, the MAGS list was developed to be inclusive of medications that are often appropriate for many medical diagnoses but may also contribute to underlying geriatric syndromes that are more chronic in nature. In addition, inclusion of such medicines increases the sensitivity of screening for medications that can be targeted through patient‐centered deprescribing efforts when clinically appropriate.

A major strength of this study is that we bring together evidence across a spectrum of geriatric syndromes commonly experienced by hospitalized elders. In addition to evaluating multiple syndromes, we applied multiple modalities; particularly the use of an iterative review process by a multidisciplinary team of experts and using Lexicomp and FDA insert packages for linking medications to specific geriatric conditions. The inclusion criteria were broadened beyond single sources of evidence in an effort to capture a comprehensive list of medications. As a result, the MAGS list can be implemented as a screening tool for deprescribing interventions and assessing medication appropriateness to address individual or clusters of geriatric syndromes within a patient.

In addition to expanding this knowledge base, clinical relevance of the MAGS list is highlighted by its application to a sample of hospitalized older adults discharged to SNFs, a cohort known to experience geriatric syndromes. In fact, 43% of patients' medications at hospital discharge were MAGS. Importantly, due to the cross‐sectional nature of this study, we cannot be certain if the medication caused or potentiated each of the geriatric syndromes. However, hospitals and SNFs are devoting major resources toward reduction of falls, avoidance of urinary catheter use, and reduction of preventable readmissions. These efforts can be complemented by considering the number of medications associated with falls, urinary incontinence, and overall MAGS burden. The striking prevalence of MAGS demonstrates a rigorous need to weigh the risks and benefits of these medications. Above all, the intent of this study is not to propose that any MAGS be reflexively stopped, but rather that the MAGS list should facilitate a holistic approach to care for the complex older adult. For example, standard therapies such as gabapentin may be appropriate for treating neuralgic pain but may also contribute to falls and urinary incontinence. Thus, alternative pain treatments could be selected in place of gabapentin for a 75‐year old patient who is experiencing recurrent falls and increasing incontinence. Therefore, the MAGS list enables a patient‐provider discussion wherein medications' therapeutic benefits can be weighed against risks posed by specific clusters of geriatric syndromes, potential impact on quality of life, and consistency with goals of care.

This study has some limitations. First, although we examined a broad number of geriatric syndromes, several other geriatric syndromes experienced by hospitalized older adults were not addressed including: fecal incontinence, insomnia, and functional impairment. These syndromes were intentionally excluded from the study a priori due to reasons of feasibility and scope. Second, unlike the Beer's 2015 criteria, the MAGS list does not sub‐classify associations of medications with geriatric syndromes for patients with specific diseases (eg, heart failure). In fact, our MAGS list included medications often indicated in treating these diagnoses. A clinician must work with the patient to weigh the disease‐specific benefits of some medications with the potential effect on geriatric syndrome symptoms and outcomes. Third, the instrument has a very high sensitivity, which was intended to generate an inclusive list of medications that enables providers to weigh risks of geriatric syndromes with the intended indication benefit. The objective is not to use this list as a reflexive tool but rather help clinicians identify a starting point to address geriatric syndromes in their patients to make patient‐centered medication decisions. Although the MAGS list is intentionally large (sensitive), the advent of advanced bioinformatics can enable MAGS to be assessed in the future for both clinical and research purposes. Fourth, FDA insert packages and Lexicomp databases report anything experienced by the patient while on the particular medication, but it might not necessarily imply a causative link. The high use of MAGS and the specific geriatric syndrome may coexist due to the high prevalence and interplay of multimorbidity, polypharmacy, and geriatric syndromes in this population. Last, the list was developed by expert panel members predominantly from a single institution, which may introduce bias. Despite these limitations, the prevalence of these medications in a sample of patients transitioning from acute to postacute care highlights the utility of the MAGS list in future clinical research and quality improvement endeavors.

In conclusion, the MAGS list provides a comprehensive and sensitive indicator of medications associated with any of 6 geriatric syndromes regardless of medication indication and appropriateness. The MAGS list provides an overall degree of medication burden with respect to geriatric syndromes and a foundation for future research to assess the relationship between the presence of geriatric syndromes and syndrome‐associated medications. The MAGS list is an important first step in summarizing the data that link medications to geriatric syndromes. Future studies are needed to broaden the analysis of MAGS for other common geriatric syndromes and to identify new and emerging medications not present during the time of this analysis. The MAGS list has the potential to facilitate deprescribing efforts needed to combat the epidemic of overprescribing that may be contributing to the burden of geriatric syndromes among older patients.

Acknowledgements

The authors thank Dr. Linda Beuscher, Dr. Patricia Blair Miller, Dr. Joseph Ouslander, Dr. William Stuart Reynolds, and Dr. Warren Taylor for providing their expertise and participating in the expert panel discussions that facilitated the development of the MAGS list. The authors also recognize the research support provided by Christopher Simon Coelho.

Disclosures: This research was supported by the Department of Health and Human Services, Centers for Medicare & Medicaid Services grant #1C1CMS331006 awarded to Principal Investigator, John F. Schnelle, PhD. Dr. Vasilevskis was supported by the National Institute on Aging of the National Institutes of Health award K23AG040157 and the Geriatric Research, Education and Clinical Center. Dr. Bell was supported by National Institute on Aging‐K award K23AG048347‐01A1. Dr. Mixon is supported by a Veterans Affairs Health Services Research & Development Career Development Award (12‐168). This research was also supported by the National Center for Advancing Translational Sciences Clinical and Translational Science award UL1TR000445. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the US Department of Health and Human Services or any of its agencies, the National Center for Advancing Translation Science, the National Institutes of Health, or the Department of Veterans Affairs. Each coauthor contributed significantly to the manuscript. Dr. Kripalani has received stock/stock options from Bioscape Digital, LLC. None of the other authors have significant conflicts of interest to report related to this project or the results reported within this article.

References
  1. Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007;55:780791.
  2. Tinetti ME, Inouye SK, Gill TM, Doucette JT. Shared risk factors for falls, incontinence, and functional dependence. Unifying the approach to geriatric syndromes. JAMA. 1995;273:13481353.
  3. Rikkert MG, Rigaud AS, Hoeyweghen RJ, Graaf J. Geriatric syndromes: medical misnomer or progress in geriatrics? Neth J Med. 2003;61:8387.
  4. Buurman BM, Hoogerduijn JG, Haan RJ, et al. Geriatric conditions in acutely hospitalized older patients: prevalence and one‐year survival and functional decline. PLoS One. 2011;6:e26951.
  5. Wang HH, Sheu JT, Shyu YI, Chang HY, Li CL. Geriatric conditions as predictors of increased number of hospital admissions and hospital bed days over one year: findings of a nationwide cohort of older adults from Taiwan. Arch Gerontol Geriatr. 2014;59:169174.
  6. Cigolle CT, Langa KM, Kabeto MU, Tian Z, Blaum CS. Geriatric conditions and disability: the Health and Retirement Study. Ann Intern Med. 2007;147:156164.
  7. Lakhan P, Jones M, Wilson A, Courtney M, Hirdes J, Gray LC. A prospective cohort study of geriatric syndromes among older medical patients admitted to acute care hospitals. J Am Geriatr Soc. 2011;59:20012008.
  8. Bell SP, Vasilevskis EE, Saraf AA, et al. Geriatric syndromes in hospitalized older adults discharged to skilled nursing facilities. J Am Geriatr Soc. 2016;64(4):715722.
  9. Allen LA, Hernandez AF, Peterson ED, et al. Discharge to a skilled nursing facility and subsequent clinical outcomes among older patients hospitalized for heart failure. Circ Heart Fail. 2011;4:293300.
  10. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993;118:219223.
  11. Flood KL, Rohlfing A, Le CV, Carr DB, Rich MW. Geriatric syndromes in elderly patients admitted to an inpatient cardiology ward. J Hosp Med. 2007;2:394400.
  12. Lund BC, Schroeder MC, Middendorff G, Brooks JM. Effect of hospitalization on inappropriate prescribing in elderly Medicare beneficiaries. J Am Geriatr Soc. 2015;63:699707.
  13. Gnjidic D, Hilmer SN, Blyth FM, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community‐dwelling older men at risk of different adverse outcomes. J Clin Epidemiol. 2012;65:989995.
  14. Best O, Gnjidic D, Hilmer SN, Naganathan V, McLachlan AJ. Investigating polypharmacy and drug burden index in hospitalised older people. Intern Med J. 2013;43:912918.
  15. Hines LE, Murphy JE. Potentially harmful drug‐drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011;9:364377.
  16. Dechanont S, Maphanta S, Butthum B, Kongkaew C. Hospital admissions/visits associated with drug‐drug interactions: a systematic review and meta‐analysis. Pharmacoepidemiol Drug Saf. 2014;23:489497.
  17. Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315:10961099.
  18. Wierenga PC, Buurman BM, Parlevliet JL, et al. Association between acute geriatric syndromes and medication‐related hospital admissions. Drugs Aging. 2012;29:691699.
  19. American Geriatrics Society Beers Criteria Update Expert P. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616631.
  20. By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:22272246.
  21. Gallagher P, O'Mahony D. STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria. Age Ageing. 2008;37:673679.
  22. Mant J, Hobbs FDR, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370:493503.
  23. U.S. Food and Drug Administration. Drugs. Available at: http://www.fda.gov/Drugs/default.htm. Accessed May 15th, 2015.
  24. Hanlon JT, Artz MB, Pieper CF, et al. Inappropriate medication use among frail elderly inpatients. Ann Pharmacother. 2004;38:914.
  25. Morandi A, Vasilevskis EE, Pandharipande PP, et al. Inappropriate medications in elderly ICU survivors: where to intervene? Arch Intern Med. 2011;171:10321034.
  26. Schmader K, Hanlon JT, Weinberger M, et al. Appropriateness of medication prescribing in ambulatory elderly patients. J Am Geriatr Soc. 1994;42:12411247.
References
  1. Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007;55:780791.
  2. Tinetti ME, Inouye SK, Gill TM, Doucette JT. Shared risk factors for falls, incontinence, and functional dependence. Unifying the approach to geriatric syndromes. JAMA. 1995;273:13481353.
  3. Rikkert MG, Rigaud AS, Hoeyweghen RJ, Graaf J. Geriatric syndromes: medical misnomer or progress in geriatrics? Neth J Med. 2003;61:8387.
  4. Buurman BM, Hoogerduijn JG, Haan RJ, et al. Geriatric conditions in acutely hospitalized older patients: prevalence and one‐year survival and functional decline. PLoS One. 2011;6:e26951.
  5. Wang HH, Sheu JT, Shyu YI, Chang HY, Li CL. Geriatric conditions as predictors of increased number of hospital admissions and hospital bed days over one year: findings of a nationwide cohort of older adults from Taiwan. Arch Gerontol Geriatr. 2014;59:169174.
  6. Cigolle CT, Langa KM, Kabeto MU, Tian Z, Blaum CS. Geriatric conditions and disability: the Health and Retirement Study. Ann Intern Med. 2007;147:156164.
  7. Lakhan P, Jones M, Wilson A, Courtney M, Hirdes J, Gray LC. A prospective cohort study of geriatric syndromes among older medical patients admitted to acute care hospitals. J Am Geriatr Soc. 2011;59:20012008.
  8. Bell SP, Vasilevskis EE, Saraf AA, et al. Geriatric syndromes in hospitalized older adults discharged to skilled nursing facilities. J Am Geriatr Soc. 2016;64(4):715722.
  9. Allen LA, Hernandez AF, Peterson ED, et al. Discharge to a skilled nursing facility and subsequent clinical outcomes among older patients hospitalized for heart failure. Circ Heart Fail. 2011;4:293300.
  10. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993;118:219223.
  11. Flood KL, Rohlfing A, Le CV, Carr DB, Rich MW. Geriatric syndromes in elderly patients admitted to an inpatient cardiology ward. J Hosp Med. 2007;2:394400.
  12. Lund BC, Schroeder MC, Middendorff G, Brooks JM. Effect of hospitalization on inappropriate prescribing in elderly Medicare beneficiaries. J Am Geriatr Soc. 2015;63:699707.
  13. Gnjidic D, Hilmer SN, Blyth FM, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community‐dwelling older men at risk of different adverse outcomes. J Clin Epidemiol. 2012;65:989995.
  14. Best O, Gnjidic D, Hilmer SN, Naganathan V, McLachlan AJ. Investigating polypharmacy and drug burden index in hospitalised older people. Intern Med J. 2013;43:912918.
  15. Hines LE, Murphy JE. Potentially harmful drug‐drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011;9:364377.
  16. Dechanont S, Maphanta S, Butthum B, Kongkaew C. Hospital admissions/visits associated with drug‐drug interactions: a systematic review and meta‐analysis. Pharmacoepidemiol Drug Saf. 2014;23:489497.
  17. Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315:10961099.
  18. Wierenga PC, Buurman BM, Parlevliet JL, et al. Association between acute geriatric syndromes and medication‐related hospital admissions. Drugs Aging. 2012;29:691699.
  19. American Geriatrics Society Beers Criteria Update Expert P. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616631.
  20. By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:22272246.
  21. Gallagher P, O'Mahony D. STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria. Age Ageing. 2008;37:673679.
  22. Mant J, Hobbs FDR, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370:493503.
  23. U.S. Food and Drug Administration. Drugs. Available at: http://www.fda.gov/Drugs/default.htm. Accessed May 15th, 2015.
  24. Hanlon JT, Artz MB, Pieper CF, et al. Inappropriate medication use among frail elderly inpatients. Ann Pharmacother. 2004;38:914.
  25. Morandi A, Vasilevskis EE, Pandharipande PP, et al. Inappropriate medications in elderly ICU survivors: where to intervene? Arch Intern Med. 2011;171:10321034.
  26. Schmader K, Hanlon JT, Weinberger M, et al. Appropriateness of medication prescribing in ambulatory elderly patients. J Am Geriatr Soc. 1994;42:12411247.
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Discharge Preparedness and Readmission

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Preparedness for hospital discharge and prediction of readmission

In recent years, US hospitals have focused on decreasing readmission rates, incented by reimbursement penalties to hospitals having excessive readmissions.[1] Gaps in the quality of care provided during transitions likely contribute to preventable readmissions.[2] One compelling quality assessment in this setting is measuring patients' discharge preparedness, using key dimensions such as understanding their instructions for medication use and follow‐up. Patient‐reported preparedness for discharge may also be useful to identify risk of readmission.

Several patient‐reported measures of preparedness for discharge exist, and herein we describe 2 measures of interest. First, the Brief‐PREPARED (B‐PREPARED) measure was derived from the longer PREPARED instrument (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services), which reflects the patient's perceived needs at discharge. In previous research, the B‐PREPARED measure predicted emergency department (ED) visits for patients who had been recently hospitalized and had a high risk for readmission.[3] Second, the Care Transitions Measure‐3 (CTM‐3) was developed by Coleman et al. as a patient‐reported measure to discriminate between patients who were more likely to have an ED visit or readmission from those who did not. CTM‐3 has also been used to evaluate hospitals' level of care coordination and for public reporting purposes.[4, 5, 6] It has been endorsed by the National Quality Forum and incorporated into the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey provided to samples of recently hospitalized US patients.[7] However, recent evidence from an inpatient cohort of cardiovascular patients suggests the CTM‐3 overinflates care transition scores compared to the longer 15‐item CTM. In that cohort, the CTM‐3 could not differentiate between patients who did or did not have repeat ED visits or readmission.[8] Thus far, the B‐PREPARED and CTM‐3 measures have not been compared to one another directly.

In addition to the development of patient‐reported measures, hospitals increasingly employ administrative algorithms to predict likelihood of readmission.[9] A commonly used measure is the LACE index (Length of stay, Acuity, Comorbidity, and Emergency department use).[10] The LACE index predicted readmission and death within 30 days of discharge in a large cohort in Canada. In 2 retrospective studies of recently hospitalized patients in the United States, the LACE index's ability to discriminate between patients readmitted or not ranged from slightly better than chance to moderate (C statistic 0.56‐0.77).[11, 12]

It is unknown whether adding patient‐reported preparedness measures to commonly used readmission prediction scores increases the ability to predict readmission risk. We sought to determine whether the B‐PREPARED and CTM‐3 measures were predictive of readmission or death, as compared to the LACE index, in a large cohort of cardiovascular patients. In addition, we sought to determine the additional predictive and discriminative ability gained from administering the B‐PREPARED and CTM‐3 measures, while adjusting for the LACE index and other clinical factors. We hypothesized that: (1) higher preparedness scores on both measures would predict lower risk of readmission or death in a cohort of patients hospitalized with cardiac diagnoses; and (2) because it provides more specific and actionable information, the B‐PREPARED would discriminate readmission more accurately than CTM‐3, after controlling for clinical factors.

METHODS

Study Setting and Design

The Vanderbilt Inpatient Cohort Study (VICS) is a prospective study of patients admitted with cardiovascular disease to Vanderbilt University Hospital. The purpose of VICS is to investigate the impact of patient and social factors on postdischarge health outcomes such as quality of life, unplanned hospital utilization, and mortality. The rationale and design of VICS are detailed elsewhere.[13] Briefly, participants completed a baseline interview while hospitalized, and follow‐up phone calls were conducted within 2 to 9 days and at approximately 30 and 90 days postdischarge. During the first follow‐up call conducted by research assistants, we collected preparedness for discharge data utilizing the 2 measures described below. After the 90‐day phone call, we collected healthcare utilization since the index admission. The study was approved by the Vanderbilt University Institutional Review Board.

Patients

Eligibility screening shortly after admission identified patients with acute decompensated heart failure (ADHF) and/or an intermediate or high likelihood of acute coronary syndrome (ACS) per a physician's review of the clinical record. Exclusion criteria included: age <18 years, non‐English speaker, unstable psychiatric illness, delirium, low likelihood of follow‐up (eg, no reliable telephone number), on hospice, or otherwise too ill to complete an interview. To be included in these analyses, patients must have completed the preparedness for discharge measurements during the first follow‐up call. Patients who died before discharge or before completing the follow‐up call were excluded.

Preparedness for Discharge Measures (Patient‐Reported Data)

Preparedness for discharge was assessed using the 11‐item B‐PREPARED and the 3‐item CTM‐3.

The B‐PREPARED measures how prepared patients felt leaving the hospital with regard to: self‐care information for medications and activity, equipment/community services needed, and confidence in managing one's health after hospitalization. The B‐PREPARED measure has good internal consistency reliability (Cronbach's = 0.76) and has been validated in patients of varying age within a week of discharge. Preparedness is the sum of responses to all 11 questions, with a range of 0 to 22. Higher scores reflect increased preparedness for discharge.[3]

The CTM‐3 asks patients to rate how well their preferences were considered regarding transitional needs, as well as their understanding of postdischarge self‐management and the purpose of their medications, each on a 4‐point response scale (strongly disagree to strongly agree). The sum of the 3 responses quantifies the patient's perception of the quality of the care transition at discharge (Cronbach's = 0.86,[14] 0.92 in a cohort similar to ours[8]). Scores range from 3 to 12, with higher score indicating more preparedness. Then, the sum is transformed to a 0 to 100 scale.[15]

Clinical Readmission Risk Measures (Medical Record Data)

The LACE index, published by Van Walraven et al.,[10] takes into account 4 categories of clinical data: length of hospital stay, acuity of event, comorbidities, and ED visits in the prior 6 months. More specifically, a diagnostic code‐based, modified version of the Charlson Comorbidity Index was used to calculate the comorbidity score. These clinical criteria were obtained from an administrative database and weighted according to the methods used by Van Walraven et al. An overall score was calculated on a scale of 0 to 19, with higher scores indicating higher risk of readmission or death within 30 days.

From medical records, we also collected patients' demographic data including age, race, and gender, and diagnosis of ACS, ADHF, or both at hospital admission.

Outcome Measures

Healthcare utilization data were obtained from the index hospital as well as outside facilities. The electronic medical records from Vanderbilt University Hospital provided information about healthcare utilization at Vanderbilt 90 days after initial discharge. We also used Vanderbilt records to see if patients were transferred to Vanderbilt from other hospitals or if patients visited other hospitals before or after enrollment. We supplemented this with patient self‐report during the follow‐up telephone calls (at 30 and 90 days after initial discharge) so that any additional ED and hospital visits could be captured. Mortality data were collected from medical records, Social Security data, and family reports. The main outcome was time to first unplanned hospital readmission or death within 30 and 90 days of discharge.

Analysis

To describe our sample, we summarized categorical variables with percentages and continuous variables with percentiles. To test for evidence of unadjusted covariate‐outcome relationships, we used Pearson 2 and Wilcoxon rank sum tests for categorical and continuous covariates, respectively.

For the primary analyses we used Cox proportional hazard models to examine the independent associations between the prespecified predictors for patient‐reported preparedness and time to first unplanned readmission or death within 30 and 90 days of discharge. For each outcome (30‐ and 90‐day readmission or death), we fit marginal models separately for each of the B‐PREPARED, CTM‐3, and LACE scores. We then fit multivariable models that used both preparedness measures as well as age, gender, race, and diagnosis (ADHF and/or ACS), variables available to clinicians when patients are admitted. When fitting the multivariable models, we did not find strong evidence of nonlinear effects; therefore, only linear effects are reported. To facilitate comparison of effects, we scaled continuous variables by their interquartile range (IQR). The associated, exponentiated regression parameter estimates may therefore be interpreted as hazard ratios for readmission or death per IQR change in each predictor. In addition to parameter estimation, we computed the C index to evaluate capacity for the model to discriminate those who were and were not readmitted or died. All analyses were conducted in R version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

From the cohort of 1239 patients (Figure 1), 64%, 28%, and 7% of patients were hospitalized with ACS, ADHF, or both, respectively (Table 1). Nearly 45% of patients were female, 83% were white, and the median age was 61 years (IQR 5269). The median length of stay was 3 days (IQR 25). The median preparedness scores were high for both B‐PREPARED (21, IQR 1822) and CTM‐3 (77.8, IQR 66.7100). A total of 211 (17%) and 380 (31%) were readmitted or died within 30 and 90 days, respectively. The completion rate for the postdischarge phone calls was 88%.

Patient Characteristics
Death or Readmission Within 30 Days Death or Readmission Within 90 Days
Not Readmitted, N = 1028 Death/Readmitted, N = 211 P Value Not Readmitted, N = 859 Death/Readmitted, N = 380 P Value
  • NOTE: Continuous variables: summarize with the 5th:25th:50th:75th:95th. Categorical variables: summarize with the percentage and (N). Abbreviations: ACS, acute coronary syndromes; ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services) CTM‐3, Care Transitions Measure‐3; LACE, Length of hospital stay, Acuity of event, Comorbidities, and ED visits in the prior 6 months; LOS, length of stay. *Pearson test. Wilcoxon test.

Gender, male 55.8% (574) 53.1% (112) 0.463* 56.3% (484) 53.2% (202) 0.298*
Female 44.2% (454) 46.9% (99) 43.7% (375) 46.8% (178)
Race, white 83.9% (860) 80.6% (170) 0.237* 86.0% (737) 77.3% (293) <0.001*
Race, nonwhite 16.1% (165) 19.4% (41) 14.0% (120) 22.7% (86)
Diagnosis ACS 68.0% (699) 46.4% (98) <0.001* 72.9% (626) 45.0% (171) <0.001*
ADHF 24.8% (255) 46.0% (97) 20.3% (174) 46.8% (178)
Both 7.2% (74) 7.6% (16) 6.9% (59) 8.2% (31)
Age 39.4:52:61:68:80 37.5:53.5:62:70:82 0.301 40:52:61:68:80 38:52:61 :70:82 0.651
LOS 1:2:3:5:10 1:3: 4:7.5:17 <0.001 1:2:3:5:9 1:3:4:7:15 <0.001
CTM‐3 55.6:66.7: 77.8:100:100 55.6:66.7:77.8:100 :100 0.305 55.6:66.7:88.9:100:100 55.6:66.7:77.8:100 :100 0.080
B‐PREPARED 12:18:21:22.:22 10:17:20:22:22 0.066 12:18:21:22:22 10:17:20 :22:22 0.030
LACE 1:4: 7:10 :14 3.5:7:10:13:17 <0.001 1:4:6: 9:14 3:7:10:13:16 <0.001
Figure 1
Study flow diagram. Abbreviations: ACS, acute coronary syndrome; ADHF, acute decompensated heart failure; VICS, Vanderbilt Inpatient Cohort Study.

B‐PREPARED and CTM‐3 were moderately correlated with one another (Spearman's = 0.40, P < 0.001). In bivariate analyses (Table 1), the association between B‐PREPARED and readmission or death was significant at 90 days (P = 0.030) but not 30 days. The CTM‐3 showed no significant association with readmission or death at either time point. The LACE score was significantly associated with rates of readmission at 30 and 90 days (P < 0.001).

Outcomes Within 30 Days of Discharge

When examining readmission or death within 30 days of discharge, simple unadjusted models 2 and 3 showed that the B‐PREPARED and LACE scores, respectively, were each significantly associated with time to first readmission or death (Table 2). Specifically, a 4‐point increase in the B‐PREPARED score was associated with a 16% decrease in the hazard of readmission or death (hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72 to 0.97). A 5‐point increase in the LACE score was associated with a 100% increase in the hazard of readmission or death (HR = 2.00, 95% CI: 1.72 to 2.32). In the multivariable model with both preparedness scores and diagnosis (model 4), the B‐PREPARED score (HR = 0.82, 95% CI: 0.70 to 0.97) was significantly associated with time to first readmission or death. In the full 30‐day model including B‐PREPARED, CTM‐3, LACE, age, gender, race, and diagnosis (model 5), only the LACE score (HR = 1.83, 95% CI: 1.54 to 2.18) was independently associated with time to readmission or death. Finally, the CTM‐3 did not predict 30‐day readmission or death in any of the models tested.

Cox Models: Time to Death or Readmission Within 30 Days of Index Hospitalization
Models HR (95% CI)* P Value C Index
  • NOTE: Abbreviations: ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services); CI, confidence interval; CTM‐3, Care Transitions Measure‐3; HR, hazard ratio; LACE, Length of hospital stay, Acuity of event, Comorbidities, and Emergency department visits in the prior 6 months.

1. CTM (per 10‐point change) 0.95 (0.88 to 1.03) 0.257 0.523
2. B‐PREPARED (per 4‐point change) 0.84 (0.72 to 0.97) 0.017 0.537
3. LACE (per 5‐point change) 2.00 (1.72 to 2.32) <0.001 0.679
4. CTM (per 10‐point change) 1.00 (0.92 to 1.10) 0.935 0.620
B‐PREPARED (per 4‐point change) 0.82 (0.70 to 0.97) 0.019
ADHF only (vs ACS only) 2.46 (1.86 to 3.26) <0.001
ADHF and ACS (vs ACS only) 1.42 (0.84 to 2.42) 0.191
5. CTM (per 10‐point change) 1.02 (0.93 to 1.11) 0.722 0.692
B‐PREPARED (per 4 point change) 0.87 (0.74 to 1.03) 0.106
LACE (per 5‐point change) 1.83 (1.54 to 2.18) <0.001
ADHF only (vs ACS only) 1.51 (1.10 to 2.08) 0.010
ADHF and ACS (vs ACS only) 0.90 (0.52 to 1.55) 0.690
Age (per 10‐year change) 1.02 (0.92 to 1.14) 0.669
Female (vs male) 1.11 (0.85 to 1.46) 0.438
Nonwhite (vs white) 0.92 (0.64 to 1.30) 0.624

Outcomes Within 90 Days of Discharge

At 90 days after discharge, again the separate unadjusted models 2 and 3 demonstrated that the B‐PREPARED and LACE scores, respectively, were each significantly associated with time to first readmission or death, whereas the CTM‐3 model only showed marginal significance (Table 3). In the multivariable model with both preparedness scores and diagnosis (model 4), results were similar to 30 days as the B‐PREPARED score was significantly associated with time to first readmission or death. Lastly, in the full model (model 5) at 90 days, again the LACE score was significantly associated with time to first readmission or death. In addition, B‐PREPARED scores were associated with a significant decrease in risk of readmission or death (HR = 0.88, 95% CI: 0.78 to 1.00); CTM‐3 scores were not independently associated with outcomes.

Cox Models: Time to Death or Readmission Within 90 Days of Index Hospitalization
Model HR (95% CI)* P Value C Index
  • NOTE: Abbreviations: ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services); CI, confidence interval; CTM‐3, Care Transitions Measure‐3; HR, hazard ratio; LACE, Length of hospital stay, Acuity of event, Comorbidities, and Emergency department visits in the prior 6 months.

1. CTM (per 10‐point change) 0.94 (0.89 to 1.00) 0.051 0.526
2. B‐PREPARED (per 4‐point change) 0.84 (0.75 to 0.94) 0.002 0.533
3. LACE (per 5‐point change) 2.03 (1.82 to 2.27) <0.001 0.683
4. CTM (per 10‐point change) 0.99 (0.93 to 1.06) 0.759 0.640
B‐PREPARED (per 4‐point change) 0.83 (0.74 to 0.94) 0.003
ADHF only (vs ACS only) 2.88 (2.33 to 3.56) <0.001
ADHF and ACS (vs ACS only) 1.62 (1.11 to 2.38) 0.013
5. CTM (per 10‐point change) 1.00 (0.94 to 1.07) 0.932 0.698
B‐PREPARED (per 4‐point change) 0.88 (0.78 to 1.00) 0.043
LACE (per 5‐point change) 1.76 (1.55 to 2.00) <0.001
ADHF only (vs ACS only) 1.76 (1.39 to 2.24) <0.001
ADHF and ACS (vs ACS only) 1.00 (0.67 to 1.50) 0.980
Age (per 10‐year change) 1.00 (0.93 to 1.09) 0.894
Female (vs male) 1.10 (0.90 to 1.35) 0.341
Nonwhite (vs white) 1.14 (0.89 to 1.47) 0.288

Tables 2 and 3 also display the C indices, or the discriminative ability of the models to differentiate whether or not a patient was readmitted or died. The range of the C index is 0.5 to 1, where values closer to 0.5 indicate random predictions and values closer to 1 indicate perfect prediction. At 30 days, the individual C indices for B‐PREPARED and CTM‐3 were only slightly better than chance (0.54 and 0.52, respectively) in their discriminative abilities. However, the C indices for the LACE score alone (0.68) and the multivariable model (0.69) including all 3 measures (ie, B‐PREPARED, CTM‐3, LACE), and clinical and demographic variables, had higher utility in discriminating patients who were readmitted/died or not. The 90‐day C indices were comparable in magnitude to those at 30 days.

DISCUSSION/CONCLUSION

In this cohort of patients hospitalized with cardiovascular disease, we compared 2 patient‐reported measures of preparedness for discharge, their association with time to death or readmission at 30 and 90 days, and their ability to discriminate patients who were or were not readmitted or died. Higher preparedness as measured by higher B‐PREPARED scores was associated with lower risk of readmission or death at 30 and 90 days after discharge in unadjusted models, and at 90 days in adjusted models. CTM‐3 was not associated with the outcome in any analyses. Lastly, the individual preparedness measures were not as strongly associated with readmission or death compared to the LACE readmission index alone.

How do our findings relate to the measurement of care transition quality? We consider 2 scenarios. First, if hospitals utilize the LACE index to predict readmission, then neither self‐reported measure of preparedness adds meaningfully to its predictive ability. However, hospital management may still find the B‐PREPARED and CTM‐3 useful as a means to direct care transition quality‐improvement efforts. These measures can instruct hospitals as to what areas their patients express the greatest difficulty or lack of preparedness and closely attend to patient needs with appropriate resources. Furthermore, the patient's perception of being prepared for discharge may be different than their actual preparedness. Their perceived preparedness may be affected by cognitive impairment, dissatisfaction with medical care, depression, lower health‐related quality of life, and lower educational attainment as demonstrated by Lau et al.[16] If a patient's perception of preparedness were low, it would behoove the clinician to investigate these other issues and address those that are mutable. Additionally, perceived preparedness may not correlate with the patient's understanding of their medical conditions, so it is imperative that clinicians provide prospective guidance about their probable postdischarge trajectory. If hospitals are not utilizing the LACE index, then perhaps using the B‐PREPARED, but not the CTM‐3, may be beneficial for predicting readmission.

How do our results fit with evidence from prior studies, and what do they mean in the context of care transitions quality? First, in the psychometric evaluation of the B‐PREPARED measure in a cohort of recently hospitalized patients, the mean score was 17.3, lower than the median of 21 in our cohort.[3] Numerous studies have utilized the CTM‐3 and the longer‐version CTM‐15. Though we cannot make a direct comparison, the median in our cohort (77.8) was on par with the means from other studies, which ranged from 63 to 82.[5, 17, 18, 19] Several studies also note ceiling effects with clusters of scores at the upper end of the scale, as did we. We conjecture that our cohort's preparedness scores may be higher because our institution has made concerted efforts to improve the discharge education for cardiovascular patients.

In a comparable patient population, the TRACE‐CORE (Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education) study is a cohort of more than 2200 patients with ACS who were administered the CTM‐15 within 1 month of discharge.[8] In that study, the median CTM‐15 score was 66.6, which is lower than our cohort. With regard to the predictive ability of the CTM‐3, they note that CTM‐3 scores did not differentiate between patients who were or were not readmitted or had emergency department visits. Our results support their concern that the CTM‐15 and by extension the CTM‐3, though adopted widely as part of HCAHPS, may not have sufficient ability to discriminate differences in patient outcomes or the quality of care transitions.

More recently, patient‐reported preparedness for discharge was assessed in a prospective cohort in Canada.[16] Lau et al. administered a single‐item measure of readiness at the time of discharge to general medicine patients, and found that lower readiness scores were also not associated with readmission or death at 30 days, when adjusted for the LACE index as we did.

We must acknowledge the limitations of our findings. First, our sample of recently discharged patients with cardiovascular disease is different than the community‐dwelling, underserved Americans hospitalized in the prior year, which served as the sample for reducing the CTM‐15 to 3 items.[5] This fact may explain why we did not find the CTM‐3 to be associated with readmission in our sample. Second, our analyses did not include extensive adjustment for patient‐related factors. Rather, our intention was to see how well the preparedness measures performed independently and compare their abilities to predict readmission, which is particularly relevant for clinicians who may not have all possible covariates in predicting readmission. Finally, because we limited the analyses to the patients who completed the B‐PREPARED and CTM‐3 measures (88% completion rate), we may not have data for: (1) very ill patients, who had a higher risk of readmission and least prepared, and were not able to answer the postdischarge phone call; and (2) very functional patients, who had a lower risk of readmission and were too busy to answer the postdischarge phone call. This may have limited the extremes in the spectrum of our sample.

Importantly, our study has several strengths. We report on the largest sample to date with results of both B‐PREPARED and CTM‐3. Moreover, we examined how these measures compared to a widely used readmission prediction tool, the LACE index. We had very high postdischarge phone call completion rates in the week following discharge. Furthermore, we had thorough assessment of readmission data through patient report, electronic medical record documentation, and collection of outside medical records.

Further research is needed to elucidate: (1) the ideal administration time of the patient‐reported measures of preparedness (before or after discharge), and (2) the challenges to the implementation of measures in healthcare systems. Remaining research questions center on the tradeoffs and barriers to implementing a longer measure like the 11‐item B‐PREPARED compared to a shorter measure like the CTM‐3. We do not know whether longer measures preclude their use by busy clinicians, though it provides more specific information about what patients feel they need at hospital discharge. Additionally, studies need to demonstrate the mutability of preparedness and the response of measures to interventions designed to improve the hospital discharge process.

In our sample of recently hospitalized cardiovascular patients, there was a statistically significant association between patient‐reported preparedness for discharged, as measured by B‐PREPARED, and readmissions/death at 30 and 90 days, but the magnitude of the association was very small. Furthermore, another patient‐reported preparedness measure, CTM‐3, was not associated with readmissions or death at either 30 or 90 days. Lastly, neither measure discriminated well between patients who were readmitted or not, and neither measure added meaningfully to the LACE index in terms of predicting 30‐ or 90‐day readmissions.

Disclosures

This study was supported by grant R01 HL109388 from the National Heart, Lung, and Blood Institute (Dr. Kripalani) and in part by grant UL1 RR024975‐01 from the National Center for Research Resources, and grant 2 UL1 TR000445‐06 from the National Center for Advancing Translational Sciences. Dr. Kripalani is a consultant to SAI Interactive and holds equity in Bioscape Digital, and is a consultant to and holds equity in PictureRx, LLC. Dr. Bell is supported by the National Institutes of Health (K23AG048347) and by the Eisenstein Women's Heart Fund. Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Geriatric Research, Education and Clinical Center. Dr. Mixon is a Veterans Affairs Health Services Research and Development Service Career Development awardee (12‐168) at the Nashville Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agency was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All authors had full access to all study data and had a significant role in writing the manuscript. The contents do not represent the views of the US Department of Veterans Affairs or the United States government. Dr. Kripalani is a consultant to and holds equity in PictureRx, LLC.

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References
  1. Centers for Medicare 9(9):598603.
  2. Graumlich JF, Novotny NL, Aldag JC. Brief scale measuring patient preparedness for hospital discharge to home: psychometric properties. J Hosp Med. 2008;3(6):446454.
  3. Coleman EA, Mahoney E, Parry C. Assessing the quality of preparation for posthospital care from the patient's perspective: the care transitions measure. Med Care. 2005;43(3):246255.
  4. Parry C, Mahoney E, Chalmers SA, Coleman EA. Assessing the quality of transitional care: further applications of the care transitions measure. Med Care. 2008;46(3):317322.
  5. Coleman EA, Parry C, Chalmers SA, Chugh A, Mahoney E. The central role of performance measurement in improving the quality of transitional care. Home Health Care Serv Q. 2007;26(4):93104.
  6. Centers for Medicare 3:e001053.
  7. Kansagara D, Englander H, Salanitro AH, et al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011;306(15):16881698.
  8. Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551557.
  9. Wang H, Robinson RD, Johnson C, et al. Using the LACE index to predict hospital readmissions in congestive heart failure patients. BMC Cardiovasc Disord. 2014;14:97.
  10. Spiva L, Hand M, VanBrackle L, McVay F. Validation of a predictive model to identify patients at high risk for hospital readmission. J Healthc Qual. 2016;38(1):3441.
  11. Meyers AG, Salanitro A, Wallston KA, et al. Determinants of health after hospital discharge: rationale and design of the Vanderbilt Inpatient Cohort Study (VICS). BMC Health Serv Res. 2014;14:10.
  12. Coleman EA. CTM frequently asked questions. Available at: http://caretransitions.org/tools-and-resources/. Accessed January 22, 2016.
  13. Coleman EA. Instructions for scoring the CTM‐3. Available at: http://caretransitions.org/tools-and-resources/. Accessed January 22, 2016.
  14. Lau D, Padwal RS, Majumdar SR, et al. Patient‐reported discharge readiness and 30‐day risk of readmission or death: a prospective cohort study. Am J Med. 2016;129:8995.
  15. Parrish MM, O'Malley K, Adams RI, Adams SR, Coleman EA. Implementaiton of the Care Transitions Intervention: sustainability and lessons learned. Prof Case Manag. 2009;14(6):282293.
  16. Englander H, Michaels L, Chan B, Kansagara D. The care transitions innovation (C‐TraIn) for socioeconomically disadvantaged adults: results of a cluster randomized controlled trial. J Gen Intern Med. 2014;29(11):14601467.
  17. Record JD, Niranjan‐Azadi A, Christmas C, et al. Telephone calls to patients after discharge from the hospital: an important part of transitions of care. Med Educ Online. 2015;29(20):26701.
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In recent years, US hospitals have focused on decreasing readmission rates, incented by reimbursement penalties to hospitals having excessive readmissions.[1] Gaps in the quality of care provided during transitions likely contribute to preventable readmissions.[2] One compelling quality assessment in this setting is measuring patients' discharge preparedness, using key dimensions such as understanding their instructions for medication use and follow‐up. Patient‐reported preparedness for discharge may also be useful to identify risk of readmission.

Several patient‐reported measures of preparedness for discharge exist, and herein we describe 2 measures of interest. First, the Brief‐PREPARED (B‐PREPARED) measure was derived from the longer PREPARED instrument (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services), which reflects the patient's perceived needs at discharge. In previous research, the B‐PREPARED measure predicted emergency department (ED) visits for patients who had been recently hospitalized and had a high risk for readmission.[3] Second, the Care Transitions Measure‐3 (CTM‐3) was developed by Coleman et al. as a patient‐reported measure to discriminate between patients who were more likely to have an ED visit or readmission from those who did not. CTM‐3 has also been used to evaluate hospitals' level of care coordination and for public reporting purposes.[4, 5, 6] It has been endorsed by the National Quality Forum and incorporated into the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey provided to samples of recently hospitalized US patients.[7] However, recent evidence from an inpatient cohort of cardiovascular patients suggests the CTM‐3 overinflates care transition scores compared to the longer 15‐item CTM. In that cohort, the CTM‐3 could not differentiate between patients who did or did not have repeat ED visits or readmission.[8] Thus far, the B‐PREPARED and CTM‐3 measures have not been compared to one another directly.

In addition to the development of patient‐reported measures, hospitals increasingly employ administrative algorithms to predict likelihood of readmission.[9] A commonly used measure is the LACE index (Length of stay, Acuity, Comorbidity, and Emergency department use).[10] The LACE index predicted readmission and death within 30 days of discharge in a large cohort in Canada. In 2 retrospective studies of recently hospitalized patients in the United States, the LACE index's ability to discriminate between patients readmitted or not ranged from slightly better than chance to moderate (C statistic 0.56‐0.77).[11, 12]

It is unknown whether adding patient‐reported preparedness measures to commonly used readmission prediction scores increases the ability to predict readmission risk. We sought to determine whether the B‐PREPARED and CTM‐3 measures were predictive of readmission or death, as compared to the LACE index, in a large cohort of cardiovascular patients. In addition, we sought to determine the additional predictive and discriminative ability gained from administering the B‐PREPARED and CTM‐3 measures, while adjusting for the LACE index and other clinical factors. We hypothesized that: (1) higher preparedness scores on both measures would predict lower risk of readmission or death in a cohort of patients hospitalized with cardiac diagnoses; and (2) because it provides more specific and actionable information, the B‐PREPARED would discriminate readmission more accurately than CTM‐3, after controlling for clinical factors.

METHODS

Study Setting and Design

The Vanderbilt Inpatient Cohort Study (VICS) is a prospective study of patients admitted with cardiovascular disease to Vanderbilt University Hospital. The purpose of VICS is to investigate the impact of patient and social factors on postdischarge health outcomes such as quality of life, unplanned hospital utilization, and mortality. The rationale and design of VICS are detailed elsewhere.[13] Briefly, participants completed a baseline interview while hospitalized, and follow‐up phone calls were conducted within 2 to 9 days and at approximately 30 and 90 days postdischarge. During the first follow‐up call conducted by research assistants, we collected preparedness for discharge data utilizing the 2 measures described below. After the 90‐day phone call, we collected healthcare utilization since the index admission. The study was approved by the Vanderbilt University Institutional Review Board.

Patients

Eligibility screening shortly after admission identified patients with acute decompensated heart failure (ADHF) and/or an intermediate or high likelihood of acute coronary syndrome (ACS) per a physician's review of the clinical record. Exclusion criteria included: age <18 years, non‐English speaker, unstable psychiatric illness, delirium, low likelihood of follow‐up (eg, no reliable telephone number), on hospice, or otherwise too ill to complete an interview. To be included in these analyses, patients must have completed the preparedness for discharge measurements during the first follow‐up call. Patients who died before discharge or before completing the follow‐up call were excluded.

Preparedness for Discharge Measures (Patient‐Reported Data)

Preparedness for discharge was assessed using the 11‐item B‐PREPARED and the 3‐item CTM‐3.

The B‐PREPARED measures how prepared patients felt leaving the hospital with regard to: self‐care information for medications and activity, equipment/community services needed, and confidence in managing one's health after hospitalization. The B‐PREPARED measure has good internal consistency reliability (Cronbach's = 0.76) and has been validated in patients of varying age within a week of discharge. Preparedness is the sum of responses to all 11 questions, with a range of 0 to 22. Higher scores reflect increased preparedness for discharge.[3]

The CTM‐3 asks patients to rate how well their preferences were considered regarding transitional needs, as well as their understanding of postdischarge self‐management and the purpose of their medications, each on a 4‐point response scale (strongly disagree to strongly agree). The sum of the 3 responses quantifies the patient's perception of the quality of the care transition at discharge (Cronbach's = 0.86,[14] 0.92 in a cohort similar to ours[8]). Scores range from 3 to 12, with higher score indicating more preparedness. Then, the sum is transformed to a 0 to 100 scale.[15]

Clinical Readmission Risk Measures (Medical Record Data)

The LACE index, published by Van Walraven et al.,[10] takes into account 4 categories of clinical data: length of hospital stay, acuity of event, comorbidities, and ED visits in the prior 6 months. More specifically, a diagnostic code‐based, modified version of the Charlson Comorbidity Index was used to calculate the comorbidity score. These clinical criteria were obtained from an administrative database and weighted according to the methods used by Van Walraven et al. An overall score was calculated on a scale of 0 to 19, with higher scores indicating higher risk of readmission or death within 30 days.

From medical records, we also collected patients' demographic data including age, race, and gender, and diagnosis of ACS, ADHF, or both at hospital admission.

Outcome Measures

Healthcare utilization data were obtained from the index hospital as well as outside facilities. The electronic medical records from Vanderbilt University Hospital provided information about healthcare utilization at Vanderbilt 90 days after initial discharge. We also used Vanderbilt records to see if patients were transferred to Vanderbilt from other hospitals or if patients visited other hospitals before or after enrollment. We supplemented this with patient self‐report during the follow‐up telephone calls (at 30 and 90 days after initial discharge) so that any additional ED and hospital visits could be captured. Mortality data were collected from medical records, Social Security data, and family reports. The main outcome was time to first unplanned hospital readmission or death within 30 and 90 days of discharge.

Analysis

To describe our sample, we summarized categorical variables with percentages and continuous variables with percentiles. To test for evidence of unadjusted covariate‐outcome relationships, we used Pearson 2 and Wilcoxon rank sum tests for categorical and continuous covariates, respectively.

For the primary analyses we used Cox proportional hazard models to examine the independent associations between the prespecified predictors for patient‐reported preparedness and time to first unplanned readmission or death within 30 and 90 days of discharge. For each outcome (30‐ and 90‐day readmission or death), we fit marginal models separately for each of the B‐PREPARED, CTM‐3, and LACE scores. We then fit multivariable models that used both preparedness measures as well as age, gender, race, and diagnosis (ADHF and/or ACS), variables available to clinicians when patients are admitted. When fitting the multivariable models, we did not find strong evidence of nonlinear effects; therefore, only linear effects are reported. To facilitate comparison of effects, we scaled continuous variables by their interquartile range (IQR). The associated, exponentiated regression parameter estimates may therefore be interpreted as hazard ratios for readmission or death per IQR change in each predictor. In addition to parameter estimation, we computed the C index to evaluate capacity for the model to discriminate those who were and were not readmitted or died. All analyses were conducted in R version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

From the cohort of 1239 patients (Figure 1), 64%, 28%, and 7% of patients were hospitalized with ACS, ADHF, or both, respectively (Table 1). Nearly 45% of patients were female, 83% were white, and the median age was 61 years (IQR 5269). The median length of stay was 3 days (IQR 25). The median preparedness scores were high for both B‐PREPARED (21, IQR 1822) and CTM‐3 (77.8, IQR 66.7100). A total of 211 (17%) and 380 (31%) were readmitted or died within 30 and 90 days, respectively. The completion rate for the postdischarge phone calls was 88%.

Patient Characteristics
Death or Readmission Within 30 Days Death or Readmission Within 90 Days
Not Readmitted, N = 1028 Death/Readmitted, N = 211 P Value Not Readmitted, N = 859 Death/Readmitted, N = 380 P Value
  • NOTE: Continuous variables: summarize with the 5th:25th:50th:75th:95th. Categorical variables: summarize with the percentage and (N). Abbreviations: ACS, acute coronary syndromes; ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services) CTM‐3, Care Transitions Measure‐3; LACE, Length of hospital stay, Acuity of event, Comorbidities, and ED visits in the prior 6 months; LOS, length of stay. *Pearson test. Wilcoxon test.

Gender, male 55.8% (574) 53.1% (112) 0.463* 56.3% (484) 53.2% (202) 0.298*
Female 44.2% (454) 46.9% (99) 43.7% (375) 46.8% (178)
Race, white 83.9% (860) 80.6% (170) 0.237* 86.0% (737) 77.3% (293) <0.001*
Race, nonwhite 16.1% (165) 19.4% (41) 14.0% (120) 22.7% (86)
Diagnosis ACS 68.0% (699) 46.4% (98) <0.001* 72.9% (626) 45.0% (171) <0.001*
ADHF 24.8% (255) 46.0% (97) 20.3% (174) 46.8% (178)
Both 7.2% (74) 7.6% (16) 6.9% (59) 8.2% (31)
Age 39.4:52:61:68:80 37.5:53.5:62:70:82 0.301 40:52:61:68:80 38:52:61 :70:82 0.651
LOS 1:2:3:5:10 1:3: 4:7.5:17 <0.001 1:2:3:5:9 1:3:4:7:15 <0.001
CTM‐3 55.6:66.7: 77.8:100:100 55.6:66.7:77.8:100 :100 0.305 55.6:66.7:88.9:100:100 55.6:66.7:77.8:100 :100 0.080
B‐PREPARED 12:18:21:22.:22 10:17:20:22:22 0.066 12:18:21:22:22 10:17:20 :22:22 0.030
LACE 1:4: 7:10 :14 3.5:7:10:13:17 <0.001 1:4:6: 9:14 3:7:10:13:16 <0.001
Figure 1
Study flow diagram. Abbreviations: ACS, acute coronary syndrome; ADHF, acute decompensated heart failure; VICS, Vanderbilt Inpatient Cohort Study.

B‐PREPARED and CTM‐3 were moderately correlated with one another (Spearman's = 0.40, P < 0.001). In bivariate analyses (Table 1), the association between B‐PREPARED and readmission or death was significant at 90 days (P = 0.030) but not 30 days. The CTM‐3 showed no significant association with readmission or death at either time point. The LACE score was significantly associated with rates of readmission at 30 and 90 days (P < 0.001).

Outcomes Within 30 Days of Discharge

When examining readmission or death within 30 days of discharge, simple unadjusted models 2 and 3 showed that the B‐PREPARED and LACE scores, respectively, were each significantly associated with time to first readmission or death (Table 2). Specifically, a 4‐point increase in the B‐PREPARED score was associated with a 16% decrease in the hazard of readmission or death (hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72 to 0.97). A 5‐point increase in the LACE score was associated with a 100% increase in the hazard of readmission or death (HR = 2.00, 95% CI: 1.72 to 2.32). In the multivariable model with both preparedness scores and diagnosis (model 4), the B‐PREPARED score (HR = 0.82, 95% CI: 0.70 to 0.97) was significantly associated with time to first readmission or death. In the full 30‐day model including B‐PREPARED, CTM‐3, LACE, age, gender, race, and diagnosis (model 5), only the LACE score (HR = 1.83, 95% CI: 1.54 to 2.18) was independently associated with time to readmission or death. Finally, the CTM‐3 did not predict 30‐day readmission or death in any of the models tested.

Cox Models: Time to Death or Readmission Within 30 Days of Index Hospitalization
Models HR (95% CI)* P Value C Index
  • NOTE: Abbreviations: ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services); CI, confidence interval; CTM‐3, Care Transitions Measure‐3; HR, hazard ratio; LACE, Length of hospital stay, Acuity of event, Comorbidities, and Emergency department visits in the prior 6 months.

1. CTM (per 10‐point change) 0.95 (0.88 to 1.03) 0.257 0.523
2. B‐PREPARED (per 4‐point change) 0.84 (0.72 to 0.97) 0.017 0.537
3. LACE (per 5‐point change) 2.00 (1.72 to 2.32) <0.001 0.679
4. CTM (per 10‐point change) 1.00 (0.92 to 1.10) 0.935 0.620
B‐PREPARED (per 4‐point change) 0.82 (0.70 to 0.97) 0.019
ADHF only (vs ACS only) 2.46 (1.86 to 3.26) <0.001
ADHF and ACS (vs ACS only) 1.42 (0.84 to 2.42) 0.191
5. CTM (per 10‐point change) 1.02 (0.93 to 1.11) 0.722 0.692
B‐PREPARED (per 4 point change) 0.87 (0.74 to 1.03) 0.106
LACE (per 5‐point change) 1.83 (1.54 to 2.18) <0.001
ADHF only (vs ACS only) 1.51 (1.10 to 2.08) 0.010
ADHF and ACS (vs ACS only) 0.90 (0.52 to 1.55) 0.690
Age (per 10‐year change) 1.02 (0.92 to 1.14) 0.669
Female (vs male) 1.11 (0.85 to 1.46) 0.438
Nonwhite (vs white) 0.92 (0.64 to 1.30) 0.624

Outcomes Within 90 Days of Discharge

At 90 days after discharge, again the separate unadjusted models 2 and 3 demonstrated that the B‐PREPARED and LACE scores, respectively, were each significantly associated with time to first readmission or death, whereas the CTM‐3 model only showed marginal significance (Table 3). In the multivariable model with both preparedness scores and diagnosis (model 4), results were similar to 30 days as the B‐PREPARED score was significantly associated with time to first readmission or death. Lastly, in the full model (model 5) at 90 days, again the LACE score was significantly associated with time to first readmission or death. In addition, B‐PREPARED scores were associated with a significant decrease in risk of readmission or death (HR = 0.88, 95% CI: 0.78 to 1.00); CTM‐3 scores were not independently associated with outcomes.

Cox Models: Time to Death or Readmission Within 90 Days of Index Hospitalization
Model HR (95% CI)* P Value C Index
  • NOTE: Abbreviations: ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services); CI, confidence interval; CTM‐3, Care Transitions Measure‐3; HR, hazard ratio; LACE, Length of hospital stay, Acuity of event, Comorbidities, and Emergency department visits in the prior 6 months.

1. CTM (per 10‐point change) 0.94 (0.89 to 1.00) 0.051 0.526
2. B‐PREPARED (per 4‐point change) 0.84 (0.75 to 0.94) 0.002 0.533
3. LACE (per 5‐point change) 2.03 (1.82 to 2.27) <0.001 0.683
4. CTM (per 10‐point change) 0.99 (0.93 to 1.06) 0.759 0.640
B‐PREPARED (per 4‐point change) 0.83 (0.74 to 0.94) 0.003
ADHF only (vs ACS only) 2.88 (2.33 to 3.56) <0.001
ADHF and ACS (vs ACS only) 1.62 (1.11 to 2.38) 0.013
5. CTM (per 10‐point change) 1.00 (0.94 to 1.07) 0.932 0.698
B‐PREPARED (per 4‐point change) 0.88 (0.78 to 1.00) 0.043
LACE (per 5‐point change) 1.76 (1.55 to 2.00) <0.001
ADHF only (vs ACS only) 1.76 (1.39 to 2.24) <0.001
ADHF and ACS (vs ACS only) 1.00 (0.67 to 1.50) 0.980
Age (per 10‐year change) 1.00 (0.93 to 1.09) 0.894
Female (vs male) 1.10 (0.90 to 1.35) 0.341
Nonwhite (vs white) 1.14 (0.89 to 1.47) 0.288

Tables 2 and 3 also display the C indices, or the discriminative ability of the models to differentiate whether or not a patient was readmitted or died. The range of the C index is 0.5 to 1, where values closer to 0.5 indicate random predictions and values closer to 1 indicate perfect prediction. At 30 days, the individual C indices for B‐PREPARED and CTM‐3 were only slightly better than chance (0.54 and 0.52, respectively) in their discriminative abilities. However, the C indices for the LACE score alone (0.68) and the multivariable model (0.69) including all 3 measures (ie, B‐PREPARED, CTM‐3, LACE), and clinical and demographic variables, had higher utility in discriminating patients who were readmitted/died or not. The 90‐day C indices were comparable in magnitude to those at 30 days.

DISCUSSION/CONCLUSION

In this cohort of patients hospitalized with cardiovascular disease, we compared 2 patient‐reported measures of preparedness for discharge, their association with time to death or readmission at 30 and 90 days, and their ability to discriminate patients who were or were not readmitted or died. Higher preparedness as measured by higher B‐PREPARED scores was associated with lower risk of readmission or death at 30 and 90 days after discharge in unadjusted models, and at 90 days in adjusted models. CTM‐3 was not associated with the outcome in any analyses. Lastly, the individual preparedness measures were not as strongly associated with readmission or death compared to the LACE readmission index alone.

How do our findings relate to the measurement of care transition quality? We consider 2 scenarios. First, if hospitals utilize the LACE index to predict readmission, then neither self‐reported measure of preparedness adds meaningfully to its predictive ability. However, hospital management may still find the B‐PREPARED and CTM‐3 useful as a means to direct care transition quality‐improvement efforts. These measures can instruct hospitals as to what areas their patients express the greatest difficulty or lack of preparedness and closely attend to patient needs with appropriate resources. Furthermore, the patient's perception of being prepared for discharge may be different than their actual preparedness. Their perceived preparedness may be affected by cognitive impairment, dissatisfaction with medical care, depression, lower health‐related quality of life, and lower educational attainment as demonstrated by Lau et al.[16] If a patient's perception of preparedness were low, it would behoove the clinician to investigate these other issues and address those that are mutable. Additionally, perceived preparedness may not correlate with the patient's understanding of their medical conditions, so it is imperative that clinicians provide prospective guidance about their probable postdischarge trajectory. If hospitals are not utilizing the LACE index, then perhaps using the B‐PREPARED, but not the CTM‐3, may be beneficial for predicting readmission.

How do our results fit with evidence from prior studies, and what do they mean in the context of care transitions quality? First, in the psychometric evaluation of the B‐PREPARED measure in a cohort of recently hospitalized patients, the mean score was 17.3, lower than the median of 21 in our cohort.[3] Numerous studies have utilized the CTM‐3 and the longer‐version CTM‐15. Though we cannot make a direct comparison, the median in our cohort (77.8) was on par with the means from other studies, which ranged from 63 to 82.[5, 17, 18, 19] Several studies also note ceiling effects with clusters of scores at the upper end of the scale, as did we. We conjecture that our cohort's preparedness scores may be higher because our institution has made concerted efforts to improve the discharge education for cardiovascular patients.

In a comparable patient population, the TRACE‐CORE (Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education) study is a cohort of more than 2200 patients with ACS who were administered the CTM‐15 within 1 month of discharge.[8] In that study, the median CTM‐15 score was 66.6, which is lower than our cohort. With regard to the predictive ability of the CTM‐3, they note that CTM‐3 scores did not differentiate between patients who were or were not readmitted or had emergency department visits. Our results support their concern that the CTM‐15 and by extension the CTM‐3, though adopted widely as part of HCAHPS, may not have sufficient ability to discriminate differences in patient outcomes or the quality of care transitions.

More recently, patient‐reported preparedness for discharge was assessed in a prospective cohort in Canada.[16] Lau et al. administered a single‐item measure of readiness at the time of discharge to general medicine patients, and found that lower readiness scores were also not associated with readmission or death at 30 days, when adjusted for the LACE index as we did.

We must acknowledge the limitations of our findings. First, our sample of recently discharged patients with cardiovascular disease is different than the community‐dwelling, underserved Americans hospitalized in the prior year, which served as the sample for reducing the CTM‐15 to 3 items.[5] This fact may explain why we did not find the CTM‐3 to be associated with readmission in our sample. Second, our analyses did not include extensive adjustment for patient‐related factors. Rather, our intention was to see how well the preparedness measures performed independently and compare their abilities to predict readmission, which is particularly relevant for clinicians who may not have all possible covariates in predicting readmission. Finally, because we limited the analyses to the patients who completed the B‐PREPARED and CTM‐3 measures (88% completion rate), we may not have data for: (1) very ill patients, who had a higher risk of readmission and least prepared, and were not able to answer the postdischarge phone call; and (2) very functional patients, who had a lower risk of readmission and were too busy to answer the postdischarge phone call. This may have limited the extremes in the spectrum of our sample.

Importantly, our study has several strengths. We report on the largest sample to date with results of both B‐PREPARED and CTM‐3. Moreover, we examined how these measures compared to a widely used readmission prediction tool, the LACE index. We had very high postdischarge phone call completion rates in the week following discharge. Furthermore, we had thorough assessment of readmission data through patient report, electronic medical record documentation, and collection of outside medical records.

Further research is needed to elucidate: (1) the ideal administration time of the patient‐reported measures of preparedness (before or after discharge), and (2) the challenges to the implementation of measures in healthcare systems. Remaining research questions center on the tradeoffs and barriers to implementing a longer measure like the 11‐item B‐PREPARED compared to a shorter measure like the CTM‐3. We do not know whether longer measures preclude their use by busy clinicians, though it provides more specific information about what patients feel they need at hospital discharge. Additionally, studies need to demonstrate the mutability of preparedness and the response of measures to interventions designed to improve the hospital discharge process.

In our sample of recently hospitalized cardiovascular patients, there was a statistically significant association between patient‐reported preparedness for discharged, as measured by B‐PREPARED, and readmissions/death at 30 and 90 days, but the magnitude of the association was very small. Furthermore, another patient‐reported preparedness measure, CTM‐3, was not associated with readmissions or death at either 30 or 90 days. Lastly, neither measure discriminated well between patients who were readmitted or not, and neither measure added meaningfully to the LACE index in terms of predicting 30‐ or 90‐day readmissions.

Disclosures

This study was supported by grant R01 HL109388 from the National Heart, Lung, and Blood Institute (Dr. Kripalani) and in part by grant UL1 RR024975‐01 from the National Center for Research Resources, and grant 2 UL1 TR000445‐06 from the National Center for Advancing Translational Sciences. Dr. Kripalani is a consultant to SAI Interactive and holds equity in Bioscape Digital, and is a consultant to and holds equity in PictureRx, LLC. Dr. Bell is supported by the National Institutes of Health (K23AG048347) and by the Eisenstein Women's Heart Fund. Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Geriatric Research, Education and Clinical Center. Dr. Mixon is a Veterans Affairs Health Services Research and Development Service Career Development awardee (12‐168) at the Nashville Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agency was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All authors had full access to all study data and had a significant role in writing the manuscript. The contents do not represent the views of the US Department of Veterans Affairs or the United States government. Dr. Kripalani is a consultant to and holds equity in PictureRx, LLC.

In recent years, US hospitals have focused on decreasing readmission rates, incented by reimbursement penalties to hospitals having excessive readmissions.[1] Gaps in the quality of care provided during transitions likely contribute to preventable readmissions.[2] One compelling quality assessment in this setting is measuring patients' discharge preparedness, using key dimensions such as understanding their instructions for medication use and follow‐up. Patient‐reported preparedness for discharge may also be useful to identify risk of readmission.

Several patient‐reported measures of preparedness for discharge exist, and herein we describe 2 measures of interest. First, the Brief‐PREPARED (B‐PREPARED) measure was derived from the longer PREPARED instrument (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services), which reflects the patient's perceived needs at discharge. In previous research, the B‐PREPARED measure predicted emergency department (ED) visits for patients who had been recently hospitalized and had a high risk for readmission.[3] Second, the Care Transitions Measure‐3 (CTM‐3) was developed by Coleman et al. as a patient‐reported measure to discriminate between patients who were more likely to have an ED visit or readmission from those who did not. CTM‐3 has also been used to evaluate hospitals' level of care coordination and for public reporting purposes.[4, 5, 6] It has been endorsed by the National Quality Forum and incorporated into the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey provided to samples of recently hospitalized US patients.[7] However, recent evidence from an inpatient cohort of cardiovascular patients suggests the CTM‐3 overinflates care transition scores compared to the longer 15‐item CTM. In that cohort, the CTM‐3 could not differentiate between patients who did or did not have repeat ED visits or readmission.[8] Thus far, the B‐PREPARED and CTM‐3 measures have not been compared to one another directly.

In addition to the development of patient‐reported measures, hospitals increasingly employ administrative algorithms to predict likelihood of readmission.[9] A commonly used measure is the LACE index (Length of stay, Acuity, Comorbidity, and Emergency department use).[10] The LACE index predicted readmission and death within 30 days of discharge in a large cohort in Canada. In 2 retrospective studies of recently hospitalized patients in the United States, the LACE index's ability to discriminate between patients readmitted or not ranged from slightly better than chance to moderate (C statistic 0.56‐0.77).[11, 12]

It is unknown whether adding patient‐reported preparedness measures to commonly used readmission prediction scores increases the ability to predict readmission risk. We sought to determine whether the B‐PREPARED and CTM‐3 measures were predictive of readmission or death, as compared to the LACE index, in a large cohort of cardiovascular patients. In addition, we sought to determine the additional predictive and discriminative ability gained from administering the B‐PREPARED and CTM‐3 measures, while adjusting for the LACE index and other clinical factors. We hypothesized that: (1) higher preparedness scores on both measures would predict lower risk of readmission or death in a cohort of patients hospitalized with cardiac diagnoses; and (2) because it provides more specific and actionable information, the B‐PREPARED would discriminate readmission more accurately than CTM‐3, after controlling for clinical factors.

METHODS

Study Setting and Design

The Vanderbilt Inpatient Cohort Study (VICS) is a prospective study of patients admitted with cardiovascular disease to Vanderbilt University Hospital. The purpose of VICS is to investigate the impact of patient and social factors on postdischarge health outcomes such as quality of life, unplanned hospital utilization, and mortality. The rationale and design of VICS are detailed elsewhere.[13] Briefly, participants completed a baseline interview while hospitalized, and follow‐up phone calls were conducted within 2 to 9 days and at approximately 30 and 90 days postdischarge. During the first follow‐up call conducted by research assistants, we collected preparedness for discharge data utilizing the 2 measures described below. After the 90‐day phone call, we collected healthcare utilization since the index admission. The study was approved by the Vanderbilt University Institutional Review Board.

Patients

Eligibility screening shortly after admission identified patients with acute decompensated heart failure (ADHF) and/or an intermediate or high likelihood of acute coronary syndrome (ACS) per a physician's review of the clinical record. Exclusion criteria included: age <18 years, non‐English speaker, unstable psychiatric illness, delirium, low likelihood of follow‐up (eg, no reliable telephone number), on hospice, or otherwise too ill to complete an interview. To be included in these analyses, patients must have completed the preparedness for discharge measurements during the first follow‐up call. Patients who died before discharge or before completing the follow‐up call were excluded.

Preparedness for Discharge Measures (Patient‐Reported Data)

Preparedness for discharge was assessed using the 11‐item B‐PREPARED and the 3‐item CTM‐3.

The B‐PREPARED measures how prepared patients felt leaving the hospital with regard to: self‐care information for medications and activity, equipment/community services needed, and confidence in managing one's health after hospitalization. The B‐PREPARED measure has good internal consistency reliability (Cronbach's = 0.76) and has been validated in patients of varying age within a week of discharge. Preparedness is the sum of responses to all 11 questions, with a range of 0 to 22. Higher scores reflect increased preparedness for discharge.[3]

The CTM‐3 asks patients to rate how well their preferences were considered regarding transitional needs, as well as their understanding of postdischarge self‐management and the purpose of their medications, each on a 4‐point response scale (strongly disagree to strongly agree). The sum of the 3 responses quantifies the patient's perception of the quality of the care transition at discharge (Cronbach's = 0.86,[14] 0.92 in a cohort similar to ours[8]). Scores range from 3 to 12, with higher score indicating more preparedness. Then, the sum is transformed to a 0 to 100 scale.[15]

Clinical Readmission Risk Measures (Medical Record Data)

The LACE index, published by Van Walraven et al.,[10] takes into account 4 categories of clinical data: length of hospital stay, acuity of event, comorbidities, and ED visits in the prior 6 months. More specifically, a diagnostic code‐based, modified version of the Charlson Comorbidity Index was used to calculate the comorbidity score. These clinical criteria were obtained from an administrative database and weighted according to the methods used by Van Walraven et al. An overall score was calculated on a scale of 0 to 19, with higher scores indicating higher risk of readmission or death within 30 days.

From medical records, we also collected patients' demographic data including age, race, and gender, and diagnosis of ACS, ADHF, or both at hospital admission.

Outcome Measures

Healthcare utilization data were obtained from the index hospital as well as outside facilities. The electronic medical records from Vanderbilt University Hospital provided information about healthcare utilization at Vanderbilt 90 days after initial discharge. We also used Vanderbilt records to see if patients were transferred to Vanderbilt from other hospitals or if patients visited other hospitals before or after enrollment. We supplemented this with patient self‐report during the follow‐up telephone calls (at 30 and 90 days after initial discharge) so that any additional ED and hospital visits could be captured. Mortality data were collected from medical records, Social Security data, and family reports. The main outcome was time to first unplanned hospital readmission or death within 30 and 90 days of discharge.

Analysis

To describe our sample, we summarized categorical variables with percentages and continuous variables with percentiles. To test for evidence of unadjusted covariate‐outcome relationships, we used Pearson 2 and Wilcoxon rank sum tests for categorical and continuous covariates, respectively.

For the primary analyses we used Cox proportional hazard models to examine the independent associations between the prespecified predictors for patient‐reported preparedness and time to first unplanned readmission or death within 30 and 90 days of discharge. For each outcome (30‐ and 90‐day readmission or death), we fit marginal models separately for each of the B‐PREPARED, CTM‐3, and LACE scores. We then fit multivariable models that used both preparedness measures as well as age, gender, race, and diagnosis (ADHF and/or ACS), variables available to clinicians when patients are admitted. When fitting the multivariable models, we did not find strong evidence of nonlinear effects; therefore, only linear effects are reported. To facilitate comparison of effects, we scaled continuous variables by their interquartile range (IQR). The associated, exponentiated regression parameter estimates may therefore be interpreted as hazard ratios for readmission or death per IQR change in each predictor. In addition to parameter estimation, we computed the C index to evaluate capacity for the model to discriminate those who were and were not readmitted or died. All analyses were conducted in R version 3.1.2 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

From the cohort of 1239 patients (Figure 1), 64%, 28%, and 7% of patients were hospitalized with ACS, ADHF, or both, respectively (Table 1). Nearly 45% of patients were female, 83% were white, and the median age was 61 years (IQR 5269). The median length of stay was 3 days (IQR 25). The median preparedness scores were high for both B‐PREPARED (21, IQR 1822) and CTM‐3 (77.8, IQR 66.7100). A total of 211 (17%) and 380 (31%) were readmitted or died within 30 and 90 days, respectively. The completion rate for the postdischarge phone calls was 88%.

Patient Characteristics
Death or Readmission Within 30 Days Death or Readmission Within 90 Days
Not Readmitted, N = 1028 Death/Readmitted, N = 211 P Value Not Readmitted, N = 859 Death/Readmitted, N = 380 P Value
  • NOTE: Continuous variables: summarize with the 5th:25th:50th:75th:95th. Categorical variables: summarize with the percentage and (N). Abbreviations: ACS, acute coronary syndromes; ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services) CTM‐3, Care Transitions Measure‐3; LACE, Length of hospital stay, Acuity of event, Comorbidities, and ED visits in the prior 6 months; LOS, length of stay. *Pearson test. Wilcoxon test.

Gender, male 55.8% (574) 53.1% (112) 0.463* 56.3% (484) 53.2% (202) 0.298*
Female 44.2% (454) 46.9% (99) 43.7% (375) 46.8% (178)
Race, white 83.9% (860) 80.6% (170) 0.237* 86.0% (737) 77.3% (293) <0.001*
Race, nonwhite 16.1% (165) 19.4% (41) 14.0% (120) 22.7% (86)
Diagnosis ACS 68.0% (699) 46.4% (98) <0.001* 72.9% (626) 45.0% (171) <0.001*
ADHF 24.8% (255) 46.0% (97) 20.3% (174) 46.8% (178)
Both 7.2% (74) 7.6% (16) 6.9% (59) 8.2% (31)
Age 39.4:52:61:68:80 37.5:53.5:62:70:82 0.301 40:52:61:68:80 38:52:61 :70:82 0.651
LOS 1:2:3:5:10 1:3: 4:7.5:17 <0.001 1:2:3:5:9 1:3:4:7:15 <0.001
CTM‐3 55.6:66.7: 77.8:100:100 55.6:66.7:77.8:100 :100 0.305 55.6:66.7:88.9:100:100 55.6:66.7:77.8:100 :100 0.080
B‐PREPARED 12:18:21:22.:22 10:17:20:22:22 0.066 12:18:21:22:22 10:17:20 :22:22 0.030
LACE 1:4: 7:10 :14 3.5:7:10:13:17 <0.001 1:4:6: 9:14 3:7:10:13:16 <0.001
Figure 1
Study flow diagram. Abbreviations: ACS, acute coronary syndrome; ADHF, acute decompensated heart failure; VICS, Vanderbilt Inpatient Cohort Study.

B‐PREPARED and CTM‐3 were moderately correlated with one another (Spearman's = 0.40, P < 0.001). In bivariate analyses (Table 1), the association between B‐PREPARED and readmission or death was significant at 90 days (P = 0.030) but not 30 days. The CTM‐3 showed no significant association with readmission or death at either time point. The LACE score was significantly associated with rates of readmission at 30 and 90 days (P < 0.001).

Outcomes Within 30 Days of Discharge

When examining readmission or death within 30 days of discharge, simple unadjusted models 2 and 3 showed that the B‐PREPARED and LACE scores, respectively, were each significantly associated with time to first readmission or death (Table 2). Specifically, a 4‐point increase in the B‐PREPARED score was associated with a 16% decrease in the hazard of readmission or death (hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72 to 0.97). A 5‐point increase in the LACE score was associated with a 100% increase in the hazard of readmission or death (HR = 2.00, 95% CI: 1.72 to 2.32). In the multivariable model with both preparedness scores and diagnosis (model 4), the B‐PREPARED score (HR = 0.82, 95% CI: 0.70 to 0.97) was significantly associated with time to first readmission or death. In the full 30‐day model including B‐PREPARED, CTM‐3, LACE, age, gender, race, and diagnosis (model 5), only the LACE score (HR = 1.83, 95% CI: 1.54 to 2.18) was independently associated with time to readmission or death. Finally, the CTM‐3 did not predict 30‐day readmission or death in any of the models tested.

Cox Models: Time to Death or Readmission Within 30 Days of Index Hospitalization
Models HR (95% CI)* P Value C Index
  • NOTE: Abbreviations: ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services); CI, confidence interval; CTM‐3, Care Transitions Measure‐3; HR, hazard ratio; LACE, Length of hospital stay, Acuity of event, Comorbidities, and Emergency department visits in the prior 6 months.

1. CTM (per 10‐point change) 0.95 (0.88 to 1.03) 0.257 0.523
2. B‐PREPARED (per 4‐point change) 0.84 (0.72 to 0.97) 0.017 0.537
3. LACE (per 5‐point change) 2.00 (1.72 to 2.32) <0.001 0.679
4. CTM (per 10‐point change) 1.00 (0.92 to 1.10) 0.935 0.620
B‐PREPARED (per 4‐point change) 0.82 (0.70 to 0.97) 0.019
ADHF only (vs ACS only) 2.46 (1.86 to 3.26) <0.001
ADHF and ACS (vs ACS only) 1.42 (0.84 to 2.42) 0.191
5. CTM (per 10‐point change) 1.02 (0.93 to 1.11) 0.722 0.692
B‐PREPARED (per 4 point change) 0.87 (0.74 to 1.03) 0.106
LACE (per 5‐point change) 1.83 (1.54 to 2.18) <0.001
ADHF only (vs ACS only) 1.51 (1.10 to 2.08) 0.010
ADHF and ACS (vs ACS only) 0.90 (0.52 to 1.55) 0.690
Age (per 10‐year change) 1.02 (0.92 to 1.14) 0.669
Female (vs male) 1.11 (0.85 to 1.46) 0.438
Nonwhite (vs white) 0.92 (0.64 to 1.30) 0.624

Outcomes Within 90 Days of Discharge

At 90 days after discharge, again the separate unadjusted models 2 and 3 demonstrated that the B‐PREPARED and LACE scores, respectively, were each significantly associated with time to first readmission or death, whereas the CTM‐3 model only showed marginal significance (Table 3). In the multivariable model with both preparedness scores and diagnosis (model 4), results were similar to 30 days as the B‐PREPARED score was significantly associated with time to first readmission or death. Lastly, in the full model (model 5) at 90 days, again the LACE score was significantly associated with time to first readmission or death. In addition, B‐PREPARED scores were associated with a significant decrease in risk of readmission or death (HR = 0.88, 95% CI: 0.78 to 1.00); CTM‐3 scores were not independently associated with outcomes.

Cox Models: Time to Death or Readmission Within 90 Days of Index Hospitalization
Model HR (95% CI)* P Value C Index
  • NOTE: Abbreviations: ADHF, acute decompensated heart failure; B‐PREPARED, Brief PREPARED (Prescriptions, Ready to re‐enter community, Education, Placement, Assurance of safety, Realistic expectations, Empowerment, Directed to appropriate services); CI, confidence interval; CTM‐3, Care Transitions Measure‐3; HR, hazard ratio; LACE, Length of hospital stay, Acuity of event, Comorbidities, and Emergency department visits in the prior 6 months.

1. CTM (per 10‐point change) 0.94 (0.89 to 1.00) 0.051 0.526
2. B‐PREPARED (per 4‐point change) 0.84 (0.75 to 0.94) 0.002 0.533
3. LACE (per 5‐point change) 2.03 (1.82 to 2.27) <0.001 0.683
4. CTM (per 10‐point change) 0.99 (0.93 to 1.06) 0.759 0.640
B‐PREPARED (per 4‐point change) 0.83 (0.74 to 0.94) 0.003
ADHF only (vs ACS only) 2.88 (2.33 to 3.56) <0.001
ADHF and ACS (vs ACS only) 1.62 (1.11 to 2.38) 0.013
5. CTM (per 10‐point change) 1.00 (0.94 to 1.07) 0.932 0.698
B‐PREPARED (per 4‐point change) 0.88 (0.78 to 1.00) 0.043
LACE (per 5‐point change) 1.76 (1.55 to 2.00) <0.001
ADHF only (vs ACS only) 1.76 (1.39 to 2.24) <0.001
ADHF and ACS (vs ACS only) 1.00 (0.67 to 1.50) 0.980
Age (per 10‐year change) 1.00 (0.93 to 1.09) 0.894
Female (vs male) 1.10 (0.90 to 1.35) 0.341
Nonwhite (vs white) 1.14 (0.89 to 1.47) 0.288

Tables 2 and 3 also display the C indices, or the discriminative ability of the models to differentiate whether or not a patient was readmitted or died. The range of the C index is 0.5 to 1, where values closer to 0.5 indicate random predictions and values closer to 1 indicate perfect prediction. At 30 days, the individual C indices for B‐PREPARED and CTM‐3 were only slightly better than chance (0.54 and 0.52, respectively) in their discriminative abilities. However, the C indices for the LACE score alone (0.68) and the multivariable model (0.69) including all 3 measures (ie, B‐PREPARED, CTM‐3, LACE), and clinical and demographic variables, had higher utility in discriminating patients who were readmitted/died or not. The 90‐day C indices were comparable in magnitude to those at 30 days.

DISCUSSION/CONCLUSION

In this cohort of patients hospitalized with cardiovascular disease, we compared 2 patient‐reported measures of preparedness for discharge, their association with time to death or readmission at 30 and 90 days, and their ability to discriminate patients who were or were not readmitted or died. Higher preparedness as measured by higher B‐PREPARED scores was associated with lower risk of readmission or death at 30 and 90 days after discharge in unadjusted models, and at 90 days in adjusted models. CTM‐3 was not associated with the outcome in any analyses. Lastly, the individual preparedness measures were not as strongly associated with readmission or death compared to the LACE readmission index alone.

How do our findings relate to the measurement of care transition quality? We consider 2 scenarios. First, if hospitals utilize the LACE index to predict readmission, then neither self‐reported measure of preparedness adds meaningfully to its predictive ability. However, hospital management may still find the B‐PREPARED and CTM‐3 useful as a means to direct care transition quality‐improvement efforts. These measures can instruct hospitals as to what areas their patients express the greatest difficulty or lack of preparedness and closely attend to patient needs with appropriate resources. Furthermore, the patient's perception of being prepared for discharge may be different than their actual preparedness. Their perceived preparedness may be affected by cognitive impairment, dissatisfaction with medical care, depression, lower health‐related quality of life, and lower educational attainment as demonstrated by Lau et al.[16] If a patient's perception of preparedness were low, it would behoove the clinician to investigate these other issues and address those that are mutable. Additionally, perceived preparedness may not correlate with the patient's understanding of their medical conditions, so it is imperative that clinicians provide prospective guidance about their probable postdischarge trajectory. If hospitals are not utilizing the LACE index, then perhaps using the B‐PREPARED, but not the CTM‐3, may be beneficial for predicting readmission.

How do our results fit with evidence from prior studies, and what do they mean in the context of care transitions quality? First, in the psychometric evaluation of the B‐PREPARED measure in a cohort of recently hospitalized patients, the mean score was 17.3, lower than the median of 21 in our cohort.[3] Numerous studies have utilized the CTM‐3 and the longer‐version CTM‐15. Though we cannot make a direct comparison, the median in our cohort (77.8) was on par with the means from other studies, which ranged from 63 to 82.[5, 17, 18, 19] Several studies also note ceiling effects with clusters of scores at the upper end of the scale, as did we. We conjecture that our cohort's preparedness scores may be higher because our institution has made concerted efforts to improve the discharge education for cardiovascular patients.

In a comparable patient population, the TRACE‐CORE (Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education) study is a cohort of more than 2200 patients with ACS who were administered the CTM‐15 within 1 month of discharge.[8] In that study, the median CTM‐15 score was 66.6, which is lower than our cohort. With regard to the predictive ability of the CTM‐3, they note that CTM‐3 scores did not differentiate between patients who were or were not readmitted or had emergency department visits. Our results support their concern that the CTM‐15 and by extension the CTM‐3, though adopted widely as part of HCAHPS, may not have sufficient ability to discriminate differences in patient outcomes or the quality of care transitions.

More recently, patient‐reported preparedness for discharge was assessed in a prospective cohort in Canada.[16] Lau et al. administered a single‐item measure of readiness at the time of discharge to general medicine patients, and found that lower readiness scores were also not associated with readmission or death at 30 days, when adjusted for the LACE index as we did.

We must acknowledge the limitations of our findings. First, our sample of recently discharged patients with cardiovascular disease is different than the community‐dwelling, underserved Americans hospitalized in the prior year, which served as the sample for reducing the CTM‐15 to 3 items.[5] This fact may explain why we did not find the CTM‐3 to be associated with readmission in our sample. Second, our analyses did not include extensive adjustment for patient‐related factors. Rather, our intention was to see how well the preparedness measures performed independently and compare their abilities to predict readmission, which is particularly relevant for clinicians who may not have all possible covariates in predicting readmission. Finally, because we limited the analyses to the patients who completed the B‐PREPARED and CTM‐3 measures (88% completion rate), we may not have data for: (1) very ill patients, who had a higher risk of readmission and least prepared, and were not able to answer the postdischarge phone call; and (2) very functional patients, who had a lower risk of readmission and were too busy to answer the postdischarge phone call. This may have limited the extremes in the spectrum of our sample.

Importantly, our study has several strengths. We report on the largest sample to date with results of both B‐PREPARED and CTM‐3. Moreover, we examined how these measures compared to a widely used readmission prediction tool, the LACE index. We had very high postdischarge phone call completion rates in the week following discharge. Furthermore, we had thorough assessment of readmission data through patient report, electronic medical record documentation, and collection of outside medical records.

Further research is needed to elucidate: (1) the ideal administration time of the patient‐reported measures of preparedness (before or after discharge), and (2) the challenges to the implementation of measures in healthcare systems. Remaining research questions center on the tradeoffs and barriers to implementing a longer measure like the 11‐item B‐PREPARED compared to a shorter measure like the CTM‐3. We do not know whether longer measures preclude their use by busy clinicians, though it provides more specific information about what patients feel they need at hospital discharge. Additionally, studies need to demonstrate the mutability of preparedness and the response of measures to interventions designed to improve the hospital discharge process.

In our sample of recently hospitalized cardiovascular patients, there was a statistically significant association between patient‐reported preparedness for discharged, as measured by B‐PREPARED, and readmissions/death at 30 and 90 days, but the magnitude of the association was very small. Furthermore, another patient‐reported preparedness measure, CTM‐3, was not associated with readmissions or death at either 30 or 90 days. Lastly, neither measure discriminated well between patients who were readmitted or not, and neither measure added meaningfully to the LACE index in terms of predicting 30‐ or 90‐day readmissions.

Disclosures

This study was supported by grant R01 HL109388 from the National Heart, Lung, and Blood Institute (Dr. Kripalani) and in part by grant UL1 RR024975‐01 from the National Center for Research Resources, and grant 2 UL1 TR000445‐06 from the National Center for Advancing Translational Sciences. Dr. Kripalani is a consultant to SAI Interactive and holds equity in Bioscape Digital, and is a consultant to and holds equity in PictureRx, LLC. Dr. Bell is supported by the National Institutes of Health (K23AG048347) and by the Eisenstein Women's Heart Fund. Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Geriatric Research, Education and Clinical Center. Dr. Mixon is a Veterans Affairs Health Services Research and Development Service Career Development awardee (12‐168) at the Nashville Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agency was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All authors had full access to all study data and had a significant role in writing the manuscript. The contents do not represent the views of the US Department of Veterans Affairs or the United States government. Dr. Kripalani is a consultant to and holds equity in PictureRx, LLC.

References
  1. Centers for Medicare 9(9):598603.
  2. Graumlich JF, Novotny NL, Aldag JC. Brief scale measuring patient preparedness for hospital discharge to home: psychometric properties. J Hosp Med. 2008;3(6):446454.
  3. Coleman EA, Mahoney E, Parry C. Assessing the quality of preparation for posthospital care from the patient's perspective: the care transitions measure. Med Care. 2005;43(3):246255.
  4. Parry C, Mahoney E, Chalmers SA, Coleman EA. Assessing the quality of transitional care: further applications of the care transitions measure. Med Care. 2008;46(3):317322.
  5. Coleman EA, Parry C, Chalmers SA, Chugh A, Mahoney E. The central role of performance measurement in improving the quality of transitional care. Home Health Care Serv Q. 2007;26(4):93104.
  6. Centers for Medicare 3:e001053.
  7. Kansagara D, Englander H, Salanitro AH, et al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011;306(15):16881698.
  8. Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551557.
  9. Wang H, Robinson RD, Johnson C, et al. Using the LACE index to predict hospital readmissions in congestive heart failure patients. BMC Cardiovasc Disord. 2014;14:97.
  10. Spiva L, Hand M, VanBrackle L, McVay F. Validation of a predictive model to identify patients at high risk for hospital readmission. J Healthc Qual. 2016;38(1):3441.
  11. Meyers AG, Salanitro A, Wallston KA, et al. Determinants of health after hospital discharge: rationale and design of the Vanderbilt Inpatient Cohort Study (VICS). BMC Health Serv Res. 2014;14:10.
  12. Coleman EA. CTM frequently asked questions. Available at: http://caretransitions.org/tools-and-resources/. Accessed January 22, 2016.
  13. Coleman EA. Instructions for scoring the CTM‐3. Available at: http://caretransitions.org/tools-and-resources/. Accessed January 22, 2016.
  14. Lau D, Padwal RS, Majumdar SR, et al. Patient‐reported discharge readiness and 30‐day risk of readmission or death: a prospective cohort study. Am J Med. 2016;129:8995.
  15. Parrish MM, O'Malley K, Adams RI, Adams SR, Coleman EA. Implementaiton of the Care Transitions Intervention: sustainability and lessons learned. Prof Case Manag. 2009;14(6):282293.
  16. Englander H, Michaels L, Chan B, Kansagara D. The care transitions innovation (C‐TraIn) for socioeconomically disadvantaged adults: results of a cluster randomized controlled trial. J Gen Intern Med. 2014;29(11):14601467.
  17. Record JD, Niranjan‐Azadi A, Christmas C, et al. Telephone calls to patients after discharge from the hospital: an important part of transitions of care. Med Educ Online. 2015;29(20):26701.
References
  1. Centers for Medicare 9(9):598603.
  2. Graumlich JF, Novotny NL, Aldag JC. Brief scale measuring patient preparedness for hospital discharge to home: psychometric properties. J Hosp Med. 2008;3(6):446454.
  3. Coleman EA, Mahoney E, Parry C. Assessing the quality of preparation for posthospital care from the patient's perspective: the care transitions measure. Med Care. 2005;43(3):246255.
  4. Parry C, Mahoney E, Chalmers SA, Coleman EA. Assessing the quality of transitional care: further applications of the care transitions measure. Med Care. 2008;46(3):317322.
  5. Coleman EA, Parry C, Chalmers SA, Chugh A, Mahoney E. The central role of performance measurement in improving the quality of transitional care. Home Health Care Serv Q. 2007;26(4):93104.
  6. Centers for Medicare 3:e001053.
  7. Kansagara D, Englander H, Salanitro AH, et al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011;306(15):16881698.
  8. Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551557.
  9. Wang H, Robinson RD, Johnson C, et al. Using the LACE index to predict hospital readmissions in congestive heart failure patients. BMC Cardiovasc Disord. 2014;14:97.
  10. Spiva L, Hand M, VanBrackle L, McVay F. Validation of a predictive model to identify patients at high risk for hospital readmission. J Healthc Qual. 2016;38(1):3441.
  11. Meyers AG, Salanitro A, Wallston KA, et al. Determinants of health after hospital discharge: rationale and design of the Vanderbilt Inpatient Cohort Study (VICS). BMC Health Serv Res. 2014;14:10.
  12. Coleman EA. CTM frequently asked questions. Available at: http://caretransitions.org/tools-and-resources/. Accessed January 22, 2016.
  13. Coleman EA. Instructions for scoring the CTM‐3. Available at: http://caretransitions.org/tools-and-resources/. Accessed January 22, 2016.
  14. Lau D, Padwal RS, Majumdar SR, et al. Patient‐reported discharge readiness and 30‐day risk of readmission or death: a prospective cohort study. Am J Med. 2016;129:8995.
  15. Parrish MM, O'Malley K, Adams RI, Adams SR, Coleman EA. Implementaiton of the Care Transitions Intervention: sustainability and lessons learned. Prof Case Manag. 2009;14(6):282293.
  16. Englander H, Michaels L, Chan B, Kansagara D. The care transitions innovation (C‐TraIn) for socioeconomically disadvantaged adults: results of a cluster randomized controlled trial. J Gen Intern Med. 2014;29(11):14601467.
  17. Record JD, Niranjan‐Azadi A, Christmas C, et al. Telephone calls to patients after discharge from the hospital: an important part of transitions of care. Med Educ Online. 2015;29(20):26701.
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Ultrabrief Delirium Assessments

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Ultrabrief delirium assessments—are they ready for primetime?

Delirium is a form of acute brain failure that affects up to 64% of older hospitalized patients and is associated with a multitude of adverse outcomes.[1] Healthcare providers, regardless of clinical setting, do not identify delirium in approximately 75% of cases.[2, 3] The paucity of brief and simple delirium assessment tools has been a barrier to improving delirium recognition.

To address this unmet need, several ultrabrief (<30 seconds) delirium assessment tools have been recently studied. In this issue of the Journal of Hospital Medicine, Fick et al. evaluated 20 individual components of the 3‐minute diagnostic interview for delirium using the Confusion Assessment Method (3D‐CAM), which was recently validated in older hospitalized patients.[4, 5] They observed that the best‐performing single‐item delirium assessment was the months of the year backward (MOTYB) task from December to January. This task assesses for inattention, a cardinal feature of delirium. Using a cutoff of 1 or more errors, the MOTYB was 83% sensitive and 69% specific for delirium.[5] By adding name the day of the week, the sensitivity increased to 93% with similar specificity (64%). This supports research by O'Regan et al., who examined MOTYB, but defined a positive screen if they could not recite the months backward from December to July perfectly. They observed a sensitivity and specificity of 84% and 90%, respectively, in older hospitalized patients.[6]

The assessment of arousal, another feature of delirium, has also garnered significant interest as another ultrabrief delirium screening method. Arousal is the patient's responsiveness to the environment and can be assessed during routine clinical care. Fick et al. observed that impaired arousal using the 3D‐CAM was 19% sensitive for delirium. This is in contrast to others who have reported sensitivities of 64% to 84%.[7, 8, 9] The difference in sensitivity may in part be explained by the method used to detect arousal. The 3D‐CAM asks, Was the patient sleep/stuporous? or Was the patient hyperviglant? Previous studies used the Richmond Agitation Sedation Scale (RASS), an arousal scale based on eye contact and physical behaviors to assess patients from 5 (coma) to +4 (combative).[10] Therefore, it is important to consider the method of arousal assessment if using this feature for delirium screening.

These ultrabrief delirium assessments would be even more clinically useful if they identified patients at high risk for adverse outcomes. In this same journal issue, 2 studies evaluated the prognostic ability of several ultrabrief delirium assessments. Zadravecz et al. observed that an abnormal RASS was a moderately good predictor of 24‐hour mortality, with an area under the receiver operating characteristic curve of 0.82.[11] Yevchak et al. observed that an abnormal RASS or MOTYB was associated with longer hospital length of stays, increased in‐hospital mortality, and need for skilled nursing.[12]

Viewed as a whole, these studies represent a significant advancement in delirium measurement and have the potential to improve this quality‐of‐care issue. However, uncertainties still exist. (1) Can these ultrabrief delirium assessments be used as standalone assessments? Based upon current data, these assessments have a significant proportion of false negative and positive rates. The effect on such misclassification on patient outcomes and healthcare utilization needs to be clarified. Because of this concern, Fick et al. recommended performing a more specific delirium assessment in those who have a positive MOTYB screen.[5] (2) What is the optimal cutoff of the MOTYB task and does this cutoff vary in different patient populations? The optimal cutoff will depend on whether or not a more sensitive test (lower error threshold) or specific test (higher error threshold) is desired. The optimal cutoff may also depend on the patient population (eg, demented versus nondemented). (3) Most important to practicing hospitalist and patients, will introducing these ultrabrief delirium assessments improve delirium recognition and improve patient outcomes? The impetus for widespread implementation of these assessments would be strengthened if healthcare providers successfully applied these assessments in clinical practice and subsequently improved outcomes.

In conclusion, the MOTYB and the assessment of arousal may be reasonable alternatives to more conventional delirium screening, especially in clinical environments with significant time constraints. However, additional research is needed to better refine these instruments to the clinical environment they will be used and determine how they impact clinical care and patient outcomes.

Disclosures

Dr. Han is supported the National Heart, Lung, and Blood Institute (K12HL109019). Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Geriatric Research, Education and Clinical Center (GRECC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. The authors report no conflicts of interest.

References
  1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911922.
  2. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131135.
  3. Han JH, Zimmerman EE, Cutler N, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16(3):193200.
  4. Marcantonio ER, Ngo LH, O'Connor M, et al. 3D‐CAM: derivation and validation of a 3‐minute diagnostic interview for CAM‐defined delirium: a cross‐sectional diagnostic test study. Ann Intern Med. 2014;161(8):554561.
  5. Fick DM, Inouye SK, Guess J, et al. Preliminary development of an ultrabrief two‐item bedside test for delirium. J Hosp Med. 2015;10(00):000000.
  6. O'Regan NA, Ryan DJ, Boland E, et al. Attention! A good bedside test for delirium? J Neurol Neurosurg Psychiatry. 2014;85(10):11221131.
  7. Chester JG, Beth Harrington M, Rudolph JL, Delirium Working Group VA. Serial administration of a modified Richmond Agitation and Sedation Scale for delirium screening. J Hosp Med. 2012;7(5):450453.
  8. Tieges Z, McGrath A, Hall RJ, Maclullich AM. Abnormal level of arousal as a predictor of delirium and inattention: an exploratory study. Am J Geriatr Psychiatry. 2013;21(12):12441253.
  9. Han JH, Vasilevskis EE, Schnelle JF, et al. The diagnostic performance of the Richmond Agitation Sedation Scale for detecting delirium in older emergency department patients. Acad Emerg Med. 2015;22(7):878882.
  10. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation‐Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):13381344.
  11. Zadravecz F, Tien L, Robertson‐Dick B, et al. Comparison of mental status scales for predicting mortality on the general wards. J Hosp Med. 2015;10(10):658663.
  12. Yevchak AM, Doherty K, Archambault E, Kelley KW, Fonda JR, Rudolph JL. The association between an ultrabrief cognitive screening in older adults and hospital outcomes. J Hosp Med. 2015;10(10):651657.
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Delirium is a form of acute brain failure that affects up to 64% of older hospitalized patients and is associated with a multitude of adverse outcomes.[1] Healthcare providers, regardless of clinical setting, do not identify delirium in approximately 75% of cases.[2, 3] The paucity of brief and simple delirium assessment tools has been a barrier to improving delirium recognition.

To address this unmet need, several ultrabrief (<30 seconds) delirium assessment tools have been recently studied. In this issue of the Journal of Hospital Medicine, Fick et al. evaluated 20 individual components of the 3‐minute diagnostic interview for delirium using the Confusion Assessment Method (3D‐CAM), which was recently validated in older hospitalized patients.[4, 5] They observed that the best‐performing single‐item delirium assessment was the months of the year backward (MOTYB) task from December to January. This task assesses for inattention, a cardinal feature of delirium. Using a cutoff of 1 or more errors, the MOTYB was 83% sensitive and 69% specific for delirium.[5] By adding name the day of the week, the sensitivity increased to 93% with similar specificity (64%). This supports research by O'Regan et al., who examined MOTYB, but defined a positive screen if they could not recite the months backward from December to July perfectly. They observed a sensitivity and specificity of 84% and 90%, respectively, in older hospitalized patients.[6]

The assessment of arousal, another feature of delirium, has also garnered significant interest as another ultrabrief delirium screening method. Arousal is the patient's responsiveness to the environment and can be assessed during routine clinical care. Fick et al. observed that impaired arousal using the 3D‐CAM was 19% sensitive for delirium. This is in contrast to others who have reported sensitivities of 64% to 84%.[7, 8, 9] The difference in sensitivity may in part be explained by the method used to detect arousal. The 3D‐CAM asks, Was the patient sleep/stuporous? or Was the patient hyperviglant? Previous studies used the Richmond Agitation Sedation Scale (RASS), an arousal scale based on eye contact and physical behaviors to assess patients from 5 (coma) to +4 (combative).[10] Therefore, it is important to consider the method of arousal assessment if using this feature for delirium screening.

These ultrabrief delirium assessments would be even more clinically useful if they identified patients at high risk for adverse outcomes. In this same journal issue, 2 studies evaluated the prognostic ability of several ultrabrief delirium assessments. Zadravecz et al. observed that an abnormal RASS was a moderately good predictor of 24‐hour mortality, with an area under the receiver operating characteristic curve of 0.82.[11] Yevchak et al. observed that an abnormal RASS or MOTYB was associated with longer hospital length of stays, increased in‐hospital mortality, and need for skilled nursing.[12]

Viewed as a whole, these studies represent a significant advancement in delirium measurement and have the potential to improve this quality‐of‐care issue. However, uncertainties still exist. (1) Can these ultrabrief delirium assessments be used as standalone assessments? Based upon current data, these assessments have a significant proportion of false negative and positive rates. The effect on such misclassification on patient outcomes and healthcare utilization needs to be clarified. Because of this concern, Fick et al. recommended performing a more specific delirium assessment in those who have a positive MOTYB screen.[5] (2) What is the optimal cutoff of the MOTYB task and does this cutoff vary in different patient populations? The optimal cutoff will depend on whether or not a more sensitive test (lower error threshold) or specific test (higher error threshold) is desired. The optimal cutoff may also depend on the patient population (eg, demented versus nondemented). (3) Most important to practicing hospitalist and patients, will introducing these ultrabrief delirium assessments improve delirium recognition and improve patient outcomes? The impetus for widespread implementation of these assessments would be strengthened if healthcare providers successfully applied these assessments in clinical practice and subsequently improved outcomes.

In conclusion, the MOTYB and the assessment of arousal may be reasonable alternatives to more conventional delirium screening, especially in clinical environments with significant time constraints. However, additional research is needed to better refine these instruments to the clinical environment they will be used and determine how they impact clinical care and patient outcomes.

Disclosures

Dr. Han is supported the National Heart, Lung, and Blood Institute (K12HL109019). Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Geriatric Research, Education and Clinical Center (GRECC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. The authors report no conflicts of interest.

Delirium is a form of acute brain failure that affects up to 64% of older hospitalized patients and is associated with a multitude of adverse outcomes.[1] Healthcare providers, regardless of clinical setting, do not identify delirium in approximately 75% of cases.[2, 3] The paucity of brief and simple delirium assessment tools has been a barrier to improving delirium recognition.

To address this unmet need, several ultrabrief (<30 seconds) delirium assessment tools have been recently studied. In this issue of the Journal of Hospital Medicine, Fick et al. evaluated 20 individual components of the 3‐minute diagnostic interview for delirium using the Confusion Assessment Method (3D‐CAM), which was recently validated in older hospitalized patients.[4, 5] They observed that the best‐performing single‐item delirium assessment was the months of the year backward (MOTYB) task from December to January. This task assesses for inattention, a cardinal feature of delirium. Using a cutoff of 1 or more errors, the MOTYB was 83% sensitive and 69% specific for delirium.[5] By adding name the day of the week, the sensitivity increased to 93% with similar specificity (64%). This supports research by O'Regan et al., who examined MOTYB, but defined a positive screen if they could not recite the months backward from December to July perfectly. They observed a sensitivity and specificity of 84% and 90%, respectively, in older hospitalized patients.[6]

The assessment of arousal, another feature of delirium, has also garnered significant interest as another ultrabrief delirium screening method. Arousal is the patient's responsiveness to the environment and can be assessed during routine clinical care. Fick et al. observed that impaired arousal using the 3D‐CAM was 19% sensitive for delirium. This is in contrast to others who have reported sensitivities of 64% to 84%.[7, 8, 9] The difference in sensitivity may in part be explained by the method used to detect arousal. The 3D‐CAM asks, Was the patient sleep/stuporous? or Was the patient hyperviglant? Previous studies used the Richmond Agitation Sedation Scale (RASS), an arousal scale based on eye contact and physical behaviors to assess patients from 5 (coma) to +4 (combative).[10] Therefore, it is important to consider the method of arousal assessment if using this feature for delirium screening.

These ultrabrief delirium assessments would be even more clinically useful if they identified patients at high risk for adverse outcomes. In this same journal issue, 2 studies evaluated the prognostic ability of several ultrabrief delirium assessments. Zadravecz et al. observed that an abnormal RASS was a moderately good predictor of 24‐hour mortality, with an area under the receiver operating characteristic curve of 0.82.[11] Yevchak et al. observed that an abnormal RASS or MOTYB was associated with longer hospital length of stays, increased in‐hospital mortality, and need for skilled nursing.[12]

Viewed as a whole, these studies represent a significant advancement in delirium measurement and have the potential to improve this quality‐of‐care issue. However, uncertainties still exist. (1) Can these ultrabrief delirium assessments be used as standalone assessments? Based upon current data, these assessments have a significant proportion of false negative and positive rates. The effect on such misclassification on patient outcomes and healthcare utilization needs to be clarified. Because of this concern, Fick et al. recommended performing a more specific delirium assessment in those who have a positive MOTYB screen.[5] (2) What is the optimal cutoff of the MOTYB task and does this cutoff vary in different patient populations? The optimal cutoff will depend on whether or not a more sensitive test (lower error threshold) or specific test (higher error threshold) is desired. The optimal cutoff may also depend on the patient population (eg, demented versus nondemented). (3) Most important to practicing hospitalist and patients, will introducing these ultrabrief delirium assessments improve delirium recognition and improve patient outcomes? The impetus for widespread implementation of these assessments would be strengthened if healthcare providers successfully applied these assessments in clinical practice and subsequently improved outcomes.

In conclusion, the MOTYB and the assessment of arousal may be reasonable alternatives to more conventional delirium screening, especially in clinical environments with significant time constraints. However, additional research is needed to better refine these instruments to the clinical environment they will be used and determine how they impact clinical care and patient outcomes.

Disclosures

Dr. Han is supported the National Heart, Lung, and Blood Institute (K12HL109019). Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Geriatric Research, Education and Clinical Center (GRECC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. The authors report no conflicts of interest.

References
  1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911922.
  2. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131135.
  3. Han JH, Zimmerman EE, Cutler N, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16(3):193200.
  4. Marcantonio ER, Ngo LH, O'Connor M, et al. 3D‐CAM: derivation and validation of a 3‐minute diagnostic interview for CAM‐defined delirium: a cross‐sectional diagnostic test study. Ann Intern Med. 2014;161(8):554561.
  5. Fick DM, Inouye SK, Guess J, et al. Preliminary development of an ultrabrief two‐item bedside test for delirium. J Hosp Med. 2015;10(00):000000.
  6. O'Regan NA, Ryan DJ, Boland E, et al. Attention! A good bedside test for delirium? J Neurol Neurosurg Psychiatry. 2014;85(10):11221131.
  7. Chester JG, Beth Harrington M, Rudolph JL, Delirium Working Group VA. Serial administration of a modified Richmond Agitation and Sedation Scale for delirium screening. J Hosp Med. 2012;7(5):450453.
  8. Tieges Z, McGrath A, Hall RJ, Maclullich AM. Abnormal level of arousal as a predictor of delirium and inattention: an exploratory study. Am J Geriatr Psychiatry. 2013;21(12):12441253.
  9. Han JH, Vasilevskis EE, Schnelle JF, et al. The diagnostic performance of the Richmond Agitation Sedation Scale for detecting delirium in older emergency department patients. Acad Emerg Med. 2015;22(7):878882.
  10. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation‐Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):13381344.
  11. Zadravecz F, Tien L, Robertson‐Dick B, et al. Comparison of mental status scales for predicting mortality on the general wards. J Hosp Med. 2015;10(10):658663.
  12. Yevchak AM, Doherty K, Archambault E, Kelley KW, Fonda JR, Rudolph JL. The association between an ultrabrief cognitive screening in older adults and hospital outcomes. J Hosp Med. 2015;10(10):651657.
References
  1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911922.
  2. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131135.
  3. Han JH, Zimmerman EE, Cutler N, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16(3):193200.
  4. Marcantonio ER, Ngo LH, O'Connor M, et al. 3D‐CAM: derivation and validation of a 3‐minute diagnostic interview for CAM‐defined delirium: a cross‐sectional diagnostic test study. Ann Intern Med. 2014;161(8):554561.
  5. Fick DM, Inouye SK, Guess J, et al. Preliminary development of an ultrabrief two‐item bedside test for delirium. J Hosp Med. 2015;10(00):000000.
  6. O'Regan NA, Ryan DJ, Boland E, et al. Attention! A good bedside test for delirium? J Neurol Neurosurg Psychiatry. 2014;85(10):11221131.
  7. Chester JG, Beth Harrington M, Rudolph JL, Delirium Working Group VA. Serial administration of a modified Richmond Agitation and Sedation Scale for delirium screening. J Hosp Med. 2012;7(5):450453.
  8. Tieges Z, McGrath A, Hall RJ, Maclullich AM. Abnormal level of arousal as a predictor of delirium and inattention: an exploratory study. Am J Geriatr Psychiatry. 2013;21(12):12441253.
  9. Han JH, Vasilevskis EE, Schnelle JF, et al. The diagnostic performance of the Richmond Agitation Sedation Scale for detecting delirium in older emergency department patients. Acad Emerg Med. 2015;22(7):878882.
  10. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation‐Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):13381344.
  11. Zadravecz F, Tien L, Robertson‐Dick B, et al. Comparison of mental status scales for predicting mortality on the general wards. J Hosp Med. 2015;10(10):658663.
  12. Yevchak AM, Doherty K, Archambault E, Kelley KW, Fonda JR, Rudolph JL. The association between an ultrabrief cognitive screening in older adults and hospital outcomes. J Hosp Med. 2015;10(10):651657.
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Address for correspondence and reprint requests: Jin H. Han, MD, Department of Emergency Medicine, Vanderbilt University Medical Center, 703 Oxford House, Nashville, TN 37232‐4700; Telephone: 615‐936‐0253; Fax: 615‐936‐1316; E‐mail: jin.h.han@vanderbilt.edu
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Simple solutions may not work for complex patients: A need for new paradigms in geriatric hospital medicine

The presence of hospitalists has been a major change in acute care in recent decades. The demographics of hospitalized patients also have changed, with a substantial increase in the proportion of patients aged 65 years and older to almost 50%. Older hospitalized patients represent a medically complex population, with multiple chronic conditions including cognitive impairment.[1] It is noteworthy that, in many US hospitals, the majority of older patients are now cared for by hospitalists without subspecialty training in geriatric medicine.[2] The convergence of these changes has led us to ask important questions about the best approach to caring for the growing population of hospitalized older patients.

The care of older hospitalized patients poses unique challenges both during and following a hospitalization event. This patient population tends to have multiple chronic conditions coupled with frequent healthcare utilization or transitions in care (eg, hospital to postacute care). In addition, geriatric syndromes are common among this group and may include: delirium, dementia, depression, functional impairment, falls, incontinence, pain, polypharmacy, and unintentional weight loss. It is also common for multiple geriatric syndromes to co‐occur (eg, falls and incontinence). The presence of one or more geriatric syndromes may complicate patient care and additionally impact outcomes, including hospitalization and mortality.[3, 4] An interdisciplinary geriatric team specifically diagnoses and treats these syndromes within the context of other presenting illnesses and comorbidities. Thus, a logical hypothesis would be that specialized geriatric consultation would improve outcomes of older hospitalized patients.

The study by Nazir et al.[5] in this issue of the Journal of Hospital Medicine explores this hypothesis, but generates more questions than answers. Briefly, the study examines a cohort of older hospitalized patients with cognitive impairment (CI). The authors compare rehospitalization and mortality outcomes among 176 patients who received geriatric consultation services (GCS) and 239 patients who received usual hospital care. Although the intervention group differed from the usual care group in meaningful ways outside of the intervention, the investigators did due diligence to adjust for these differences in their analysis. After adjustment, 30‐day and 1‐year mortality outcomes were comparable between groups, and the hazard for 30‐day readmissions was higher for the GCS group.

These findings stood contrary to the authors' hypothesis and what many would expect with subspecialty involvement during hospitalization. As the authors point out, however, we should interpret these findings cautiously due to a number of factors that may contribute to the seemingly limited effect of GCS in this study. First, it is important to note that this study occurred between 2006 and 2008. The emphasis on hospital readmissions as an important clinical outcome was increasing, although it had not reached the level that followed the 2009 publication by Jencks et al.[6] This emphasis further intensified following the inclusion of the Hospital Readmissions Reduction Program (HRRP) as part of the Affordable Care Act.[7] Thus, the implementation of the GCS in this university‐affiliated hospital may have reflected this pre‐HRRP period. For example, the team‐based rounds occurred only at the time of the initial consult. If a similar GCS were designed today in the post‐HRRP period, one could imagine more intense team‐based involvement occurring throughout the hospital stay, in particular near the time of discharge. In addition, recent studies underscore the importance of supporting transitions in care for older adults, who are often in need of postacute care, home health, and other services following hospitalization.[8] As noted by Nazir and colleagues, other interventions that have shown an impact on 30‐day readmissions were multifaceted and included personnel who provide bridging between the hospital and outpatient setting. The authors also mentioned that a future component of preventing hospital readmissions was a stronger emphasis on advance care planning (ACP) discussions both during and following hospitalization. Neither of these key elements (eg, care transition personnel or proactive ACP discussions) was part of the GCS model evaluated in this study. Thus, it is unknown to what extent the higher 30‐day readmissions that occurred for the GCS group were consistent with patient/family goals of care. It is also unknown to what extent these readmissions were potentially unavoidable.

Perhaps even more importantly, this study is a reminder of the difference between efficacy and effectiveness; that is, does geriatric consultation work (efficacy) versus does a GCS as implemented at this specific hospital work (effectiveness)? The latter reflects not only aspects of what a geriatric interdisciplinary team may diagnose and recommend, but includes how patients are identified for consultation (referral process), the environment in which the consultation occurs (care coordination on unit or among team), and the fidelity to GCS recommendations. Without reported measures, it is unclear to what extent GCS achieved better recognition and treatment of geriatric syndromes, a reduction in polypharmacy, and optimal discharge planning. Theoretically, it is through the robust implementation of these components that better clinical outcomes would result. Even with a high degree of intervention implementation, 12‐month outcomes may be too far removed from the GCS intervention, especially for older patients with CI who are at high risk for decline.

Unfortunately, geriatric syndromes often go unrecognized, with high rates of polypharmacy at hospital discharge[9] and more than 50% of inpatients with unrecognized dementia,[10] delirium,[11] depression,[12] and nutritional risk.[13] Thus, our need for hospital geriatric care and expertise is greater than ever. This study highlights many of the challenges of the traditional consultative model of care and a need for innovative approaches to recognize and treat geriatric syndromes. It is likely that, given the complex nature of geriatric patients, efficacious consultative models will need to address multiple chronic conditions and extend beyond the hospital discharge period. However, based on available evidence, it is currently unclear what specific interventions are efficacious and what type of geriatric consultative model is required. No matter the method, hospitalists must recognize the unique challenges of this population and work to ensure safe hospitalization and care transitions.

Acknowledgements

The authors acknowledge John Schnelle, PhD, for his input and review of the editorial.

Disclosures: Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Tennessee Valley VA Geriatric Research, Education and Clinical Center (GRECC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans' Affairs.

References
  1. Wier L, Pfuntner A, Steiner C. Hospital Utilization Among Oldest Adults, 2008. HCUP statistical brief 103. Rockville, MD: Agency for Healthcare Research and Quality; 2010:111. Available at: http://www.hcup‐us.ahrq.gov/reports/statbriefs/sb103.pdf. Last accessed Dec 27, 2015.
  2. Kuo Y‐F, Sharma G, Freeman JL, Goodwin JS. Growth in the care of older patients by hospitalists in the United States. N Engl J Med. 2009;360(11):11021112.
  3. Wang S‐Y, Shamliyan TA, Talley KMC, Ramakrishnan R, Kane RL. Not just specific diseases: systematic review of the association of geriatric syndromes with hospitalization or nursing home admission. Arch Gerontol Geriatr. 2013;57(1):1626.
  4. Kane RL, Shamliyan T, Talley K, Pacala J. The association between geriatric syndromes and survival. J Am Geriatr Soc. 2012;60(5):896904.
  5. Nazir A, Khan B, Counsell S, Henderson M, Gao S, Boustani M. Impact of an inpatient geriatric consultative service on outcomes for cognitively impaired patients. J Hosp Med. 2015;10(5):275280.
  6. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee‐for‐service program. N Engl J Med. 2009;360(14):14181428.
  7. Patient Protection and Affordable Care Act of 2010. Hospital Readmissions Reduction Program; 2010. Pub L No. 111‐148, 124 Stat 408, S3025.
  8. Verhaegh KJ, MacNeil‐Vroomen JL, Eslami S, Geerlings SE, Rooij SE de Buurman BM. Transitional care interventions prevent hospital readmissions for adults with chronic illnesses. Health Aff (Millwood). 2014;33(9):15311539.
  9. Rohrer JE, Garrison G, Oberhelman SA, Meunier MR. Epidemiology of polypharmacy among family medicine patients at hospital discharge. J Prim Care Community Health. 2013;4(2):101105.
  10. Boustani M, Baker MS, Campbell N, et al. Impact and recognition of cognitive impairment among hospitalized elders. J Hosp Med. 2010;5(2):6975.
  11. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131135.
  12. Cepoiu M, McCusker J, Cole MG, Sewitch M, Ciampi A. Recognition of depression in older medical inpatients. J Gen Intern Med. 2007;22(5):559564.
  13. Buys DR, Roth DL, Ritchie CS, et al. Nutritional risk and body mass index predict hospitalization, nursing home admissions, and mortality in community‐dwelling older adults: results from the UAB Study of Aging with 8.5 years of follow‐up. J Gerontol A Biol Sci Med Sci. 2014;69(9):11461153.
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The presence of hospitalists has been a major change in acute care in recent decades. The demographics of hospitalized patients also have changed, with a substantial increase in the proportion of patients aged 65 years and older to almost 50%. Older hospitalized patients represent a medically complex population, with multiple chronic conditions including cognitive impairment.[1] It is noteworthy that, in many US hospitals, the majority of older patients are now cared for by hospitalists without subspecialty training in geriatric medicine.[2] The convergence of these changes has led us to ask important questions about the best approach to caring for the growing population of hospitalized older patients.

The care of older hospitalized patients poses unique challenges both during and following a hospitalization event. This patient population tends to have multiple chronic conditions coupled with frequent healthcare utilization or transitions in care (eg, hospital to postacute care). In addition, geriatric syndromes are common among this group and may include: delirium, dementia, depression, functional impairment, falls, incontinence, pain, polypharmacy, and unintentional weight loss. It is also common for multiple geriatric syndromes to co‐occur (eg, falls and incontinence). The presence of one or more geriatric syndromes may complicate patient care and additionally impact outcomes, including hospitalization and mortality.[3, 4] An interdisciplinary geriatric team specifically diagnoses and treats these syndromes within the context of other presenting illnesses and comorbidities. Thus, a logical hypothesis would be that specialized geriatric consultation would improve outcomes of older hospitalized patients.

The study by Nazir et al.[5] in this issue of the Journal of Hospital Medicine explores this hypothesis, but generates more questions than answers. Briefly, the study examines a cohort of older hospitalized patients with cognitive impairment (CI). The authors compare rehospitalization and mortality outcomes among 176 patients who received geriatric consultation services (GCS) and 239 patients who received usual hospital care. Although the intervention group differed from the usual care group in meaningful ways outside of the intervention, the investigators did due diligence to adjust for these differences in their analysis. After adjustment, 30‐day and 1‐year mortality outcomes were comparable between groups, and the hazard for 30‐day readmissions was higher for the GCS group.

These findings stood contrary to the authors' hypothesis and what many would expect with subspecialty involvement during hospitalization. As the authors point out, however, we should interpret these findings cautiously due to a number of factors that may contribute to the seemingly limited effect of GCS in this study. First, it is important to note that this study occurred between 2006 and 2008. The emphasis on hospital readmissions as an important clinical outcome was increasing, although it had not reached the level that followed the 2009 publication by Jencks et al.[6] This emphasis further intensified following the inclusion of the Hospital Readmissions Reduction Program (HRRP) as part of the Affordable Care Act.[7] Thus, the implementation of the GCS in this university‐affiliated hospital may have reflected this pre‐HRRP period. For example, the team‐based rounds occurred only at the time of the initial consult. If a similar GCS were designed today in the post‐HRRP period, one could imagine more intense team‐based involvement occurring throughout the hospital stay, in particular near the time of discharge. In addition, recent studies underscore the importance of supporting transitions in care for older adults, who are often in need of postacute care, home health, and other services following hospitalization.[8] As noted by Nazir and colleagues, other interventions that have shown an impact on 30‐day readmissions were multifaceted and included personnel who provide bridging between the hospital and outpatient setting. The authors also mentioned that a future component of preventing hospital readmissions was a stronger emphasis on advance care planning (ACP) discussions both during and following hospitalization. Neither of these key elements (eg, care transition personnel or proactive ACP discussions) was part of the GCS model evaluated in this study. Thus, it is unknown to what extent the higher 30‐day readmissions that occurred for the GCS group were consistent with patient/family goals of care. It is also unknown to what extent these readmissions were potentially unavoidable.

Perhaps even more importantly, this study is a reminder of the difference between efficacy and effectiveness; that is, does geriatric consultation work (efficacy) versus does a GCS as implemented at this specific hospital work (effectiveness)? The latter reflects not only aspects of what a geriatric interdisciplinary team may diagnose and recommend, but includes how patients are identified for consultation (referral process), the environment in which the consultation occurs (care coordination on unit or among team), and the fidelity to GCS recommendations. Without reported measures, it is unclear to what extent GCS achieved better recognition and treatment of geriatric syndromes, a reduction in polypharmacy, and optimal discharge planning. Theoretically, it is through the robust implementation of these components that better clinical outcomes would result. Even with a high degree of intervention implementation, 12‐month outcomes may be too far removed from the GCS intervention, especially for older patients with CI who are at high risk for decline.

Unfortunately, geriatric syndromes often go unrecognized, with high rates of polypharmacy at hospital discharge[9] and more than 50% of inpatients with unrecognized dementia,[10] delirium,[11] depression,[12] and nutritional risk.[13] Thus, our need for hospital geriatric care and expertise is greater than ever. This study highlights many of the challenges of the traditional consultative model of care and a need for innovative approaches to recognize and treat geriatric syndromes. It is likely that, given the complex nature of geriatric patients, efficacious consultative models will need to address multiple chronic conditions and extend beyond the hospital discharge period. However, based on available evidence, it is currently unclear what specific interventions are efficacious and what type of geriatric consultative model is required. No matter the method, hospitalists must recognize the unique challenges of this population and work to ensure safe hospitalization and care transitions.

Acknowledgements

The authors acknowledge John Schnelle, PhD, for his input and review of the editorial.

Disclosures: Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Tennessee Valley VA Geriatric Research, Education and Clinical Center (GRECC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans' Affairs.

The presence of hospitalists has been a major change in acute care in recent decades. The demographics of hospitalized patients also have changed, with a substantial increase in the proportion of patients aged 65 years and older to almost 50%. Older hospitalized patients represent a medically complex population, with multiple chronic conditions including cognitive impairment.[1] It is noteworthy that, in many US hospitals, the majority of older patients are now cared for by hospitalists without subspecialty training in geriatric medicine.[2] The convergence of these changes has led us to ask important questions about the best approach to caring for the growing population of hospitalized older patients.

The care of older hospitalized patients poses unique challenges both during and following a hospitalization event. This patient population tends to have multiple chronic conditions coupled with frequent healthcare utilization or transitions in care (eg, hospital to postacute care). In addition, geriatric syndromes are common among this group and may include: delirium, dementia, depression, functional impairment, falls, incontinence, pain, polypharmacy, and unintentional weight loss. It is also common for multiple geriatric syndromes to co‐occur (eg, falls and incontinence). The presence of one or more geriatric syndromes may complicate patient care and additionally impact outcomes, including hospitalization and mortality.[3, 4] An interdisciplinary geriatric team specifically diagnoses and treats these syndromes within the context of other presenting illnesses and comorbidities. Thus, a logical hypothesis would be that specialized geriatric consultation would improve outcomes of older hospitalized patients.

The study by Nazir et al.[5] in this issue of the Journal of Hospital Medicine explores this hypothesis, but generates more questions than answers. Briefly, the study examines a cohort of older hospitalized patients with cognitive impairment (CI). The authors compare rehospitalization and mortality outcomes among 176 patients who received geriatric consultation services (GCS) and 239 patients who received usual hospital care. Although the intervention group differed from the usual care group in meaningful ways outside of the intervention, the investigators did due diligence to adjust for these differences in their analysis. After adjustment, 30‐day and 1‐year mortality outcomes were comparable between groups, and the hazard for 30‐day readmissions was higher for the GCS group.

These findings stood contrary to the authors' hypothesis and what many would expect with subspecialty involvement during hospitalization. As the authors point out, however, we should interpret these findings cautiously due to a number of factors that may contribute to the seemingly limited effect of GCS in this study. First, it is important to note that this study occurred between 2006 and 2008. The emphasis on hospital readmissions as an important clinical outcome was increasing, although it had not reached the level that followed the 2009 publication by Jencks et al.[6] This emphasis further intensified following the inclusion of the Hospital Readmissions Reduction Program (HRRP) as part of the Affordable Care Act.[7] Thus, the implementation of the GCS in this university‐affiliated hospital may have reflected this pre‐HRRP period. For example, the team‐based rounds occurred only at the time of the initial consult. If a similar GCS were designed today in the post‐HRRP period, one could imagine more intense team‐based involvement occurring throughout the hospital stay, in particular near the time of discharge. In addition, recent studies underscore the importance of supporting transitions in care for older adults, who are often in need of postacute care, home health, and other services following hospitalization.[8] As noted by Nazir and colleagues, other interventions that have shown an impact on 30‐day readmissions were multifaceted and included personnel who provide bridging between the hospital and outpatient setting. The authors also mentioned that a future component of preventing hospital readmissions was a stronger emphasis on advance care planning (ACP) discussions both during and following hospitalization. Neither of these key elements (eg, care transition personnel or proactive ACP discussions) was part of the GCS model evaluated in this study. Thus, it is unknown to what extent the higher 30‐day readmissions that occurred for the GCS group were consistent with patient/family goals of care. It is also unknown to what extent these readmissions were potentially unavoidable.

Perhaps even more importantly, this study is a reminder of the difference between efficacy and effectiveness; that is, does geriatric consultation work (efficacy) versus does a GCS as implemented at this specific hospital work (effectiveness)? The latter reflects not only aspects of what a geriatric interdisciplinary team may diagnose and recommend, but includes how patients are identified for consultation (referral process), the environment in which the consultation occurs (care coordination on unit or among team), and the fidelity to GCS recommendations. Without reported measures, it is unclear to what extent GCS achieved better recognition and treatment of geriatric syndromes, a reduction in polypharmacy, and optimal discharge planning. Theoretically, it is through the robust implementation of these components that better clinical outcomes would result. Even with a high degree of intervention implementation, 12‐month outcomes may be too far removed from the GCS intervention, especially for older patients with CI who are at high risk for decline.

Unfortunately, geriatric syndromes often go unrecognized, with high rates of polypharmacy at hospital discharge[9] and more than 50% of inpatients with unrecognized dementia,[10] delirium,[11] depression,[12] and nutritional risk.[13] Thus, our need for hospital geriatric care and expertise is greater than ever. This study highlights many of the challenges of the traditional consultative model of care and a need for innovative approaches to recognize and treat geriatric syndromes. It is likely that, given the complex nature of geriatric patients, efficacious consultative models will need to address multiple chronic conditions and extend beyond the hospital discharge period. However, based on available evidence, it is currently unclear what specific interventions are efficacious and what type of geriatric consultative model is required. No matter the method, hospitalists must recognize the unique challenges of this population and work to ensure safe hospitalization and care transitions.

Acknowledgements

The authors acknowledge John Schnelle, PhD, for his input and review of the editorial.

Disclosures: Dr. Vasilevskis is supported by the National Institutes of Health (K23AG040157) and the Tennessee Valley VA Geriatric Research, Education and Clinical Center (GRECC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans' Affairs.

References
  1. Wier L, Pfuntner A, Steiner C. Hospital Utilization Among Oldest Adults, 2008. HCUP statistical brief 103. Rockville, MD: Agency for Healthcare Research and Quality; 2010:111. Available at: http://www.hcup‐us.ahrq.gov/reports/statbriefs/sb103.pdf. Last accessed Dec 27, 2015.
  2. Kuo Y‐F, Sharma G, Freeman JL, Goodwin JS. Growth in the care of older patients by hospitalists in the United States. N Engl J Med. 2009;360(11):11021112.
  3. Wang S‐Y, Shamliyan TA, Talley KMC, Ramakrishnan R, Kane RL. Not just specific diseases: systematic review of the association of geriatric syndromes with hospitalization or nursing home admission. Arch Gerontol Geriatr. 2013;57(1):1626.
  4. Kane RL, Shamliyan T, Talley K, Pacala J. The association between geriatric syndromes and survival. J Am Geriatr Soc. 2012;60(5):896904.
  5. Nazir A, Khan B, Counsell S, Henderson M, Gao S, Boustani M. Impact of an inpatient geriatric consultative service on outcomes for cognitively impaired patients. J Hosp Med. 2015;10(5):275280.
  6. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee‐for‐service program. N Engl J Med. 2009;360(14):14181428.
  7. Patient Protection and Affordable Care Act of 2010. Hospital Readmissions Reduction Program; 2010. Pub L No. 111‐148, 124 Stat 408, S3025.
  8. Verhaegh KJ, MacNeil‐Vroomen JL, Eslami S, Geerlings SE, Rooij SE de Buurman BM. Transitional care interventions prevent hospital readmissions for adults with chronic illnesses. Health Aff (Millwood). 2014;33(9):15311539.
  9. Rohrer JE, Garrison G, Oberhelman SA, Meunier MR. Epidemiology of polypharmacy among family medicine patients at hospital discharge. J Prim Care Community Health. 2013;4(2):101105.
  10. Boustani M, Baker MS, Campbell N, et al. Impact and recognition of cognitive impairment among hospitalized elders. J Hosp Med. 2010;5(2):6975.
  11. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131135.
  12. Cepoiu M, McCusker J, Cole MG, Sewitch M, Ciampi A. Recognition of depression in older medical inpatients. J Gen Intern Med. 2007;22(5):559564.
  13. Buys DR, Roth DL, Ritchie CS, et al. Nutritional risk and body mass index predict hospitalization, nursing home admissions, and mortality in community‐dwelling older adults: results from the UAB Study of Aging with 8.5 years of follow‐up. J Gerontol A Biol Sci Med Sci. 2014;69(9):11461153.
References
  1. Wier L, Pfuntner A, Steiner C. Hospital Utilization Among Oldest Adults, 2008. HCUP statistical brief 103. Rockville, MD: Agency for Healthcare Research and Quality; 2010:111. Available at: http://www.hcup‐us.ahrq.gov/reports/statbriefs/sb103.pdf. Last accessed Dec 27, 2015.
  2. Kuo Y‐F, Sharma G, Freeman JL, Goodwin JS. Growth in the care of older patients by hospitalists in the United States. N Engl J Med. 2009;360(11):11021112.
  3. Wang S‐Y, Shamliyan TA, Talley KMC, Ramakrishnan R, Kane RL. Not just specific diseases: systematic review of the association of geriatric syndromes with hospitalization or nursing home admission. Arch Gerontol Geriatr. 2013;57(1):1626.
  4. Kane RL, Shamliyan T, Talley K, Pacala J. The association between geriatric syndromes and survival. J Am Geriatr Soc. 2012;60(5):896904.
  5. Nazir A, Khan B, Counsell S, Henderson M, Gao S, Boustani M. Impact of an inpatient geriatric consultative service on outcomes for cognitively impaired patients. J Hosp Med. 2015;10(5):275280.
  6. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee‐for‐service program. N Engl J Med. 2009;360(14):14181428.
  7. Patient Protection and Affordable Care Act of 2010. Hospital Readmissions Reduction Program; 2010. Pub L No. 111‐148, 124 Stat 408, S3025.
  8. Verhaegh KJ, MacNeil‐Vroomen JL, Eslami S, Geerlings SE, Rooij SE de Buurman BM. Transitional care interventions prevent hospital readmissions for adults with chronic illnesses. Health Aff (Millwood). 2014;33(9):15311539.
  9. Rohrer JE, Garrison G, Oberhelman SA, Meunier MR. Epidemiology of polypharmacy among family medicine patients at hospital discharge. J Prim Care Community Health. 2013;4(2):101105.
  10. Boustani M, Baker MS, Campbell N, et al. Impact and recognition of cognitive impairment among hospitalized elders. J Hosp Med. 2010;5(2):6975.
  11. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131135.
  12. Cepoiu M, McCusker J, Cole MG, Sewitch M, Ciampi A. Recognition of depression in older medical inpatients. J Gen Intern Med. 2007;22(5):559564.
  13. Buys DR, Roth DL, Ritchie CS, et al. Nutritional risk and body mass index predict hospitalization, nursing home admissions, and mortality in community‐dwelling older adults: results from the UAB Study of Aging with 8.5 years of follow‐up. J Gerontol A Biol Sci Med Sci. 2014;69(9):11461153.
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Address for correspondence and reprint requests: Eduard E. Vasilevskis MD MPH. Vanderbilt University, 1215 21st Ave. S., 6006 MCE NT, Nashville, TN 37232‐8300; Telephone: 615‐936‐1935; Fax: 615‐936‐1269; E‐mail: eduard.vasilevskis@vanderbilt.edu.
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Impaired Arousal and Mortality

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Impaired arousal at initial presentation predicts 6‐month mortality: An analysis of 1084 acutely ill older patients

Arousal is defined as the patient's overall level of responsiveness to the environment. Its assessment is standard of care in most intensive care units (ICUs) to monitor depth of sedation and underlying brain dysfunction. There has been recent interest in expanding the role of arousal assessment beyond the ICU. Specifically, the Veterans Affairs Delirium Working Group proposed that simple arousal assessment be a vital sign to quantify underlying brain dysfunction.[1] The rationale is that impaired arousal is closely linked with delirium,[2] and is an integral component of multiple delirium assessments.[3, 4, 5] Chester et al. observed that the presence of impaired arousal was 64% sensitive and 93% specific for delirium diagnosed by a psychiatrist.[2] Delirium is an under‐recognized public health problem that affects up to 25% of older hospitalized patients,[6, 7] is associated with a multitude of adverse outcomes such as death and accelerated cognitive decline,[8] and costs the US healthcare system an excess of $152 billion dollars.[9]

Most delirium assessments require the patient to undergo additional cognitive testing. The assessment of arousal, however, requires the rater to merely observe the patient during routine clinical care and can be easily integrated into the clinical workflow.[10] Because of its simplicity and brevity, assessing arousal alone using validated scales such as the Richmond Agitation‐Sedation Scale (RASS) may be a more appealing alternative to traditional, more complex delirium screening in the acute care setting. Its clinical utility would be further strengthened if impaired arousal was also associated with mortality, and conferred risk even in the absence of delirium. As a result, we sought to determine if impaired arousal at initial presentation in older acutely ill patients predicted 6‐month mortality and whether this relationship was present in the absence of delirium.

METHODS

Design Overview

We performed a planned secondary analysis of 2 prospective cohorts that enrolled patients from May 2007 to August 2008 between 8 am and 10 pm during the weekdays, and July 2009 to February 2012 between 8 am and 4 pm during the weekdays. The first cohort was designed to evaluate the relationship between delirium and patient outcomes.[11, 12] The second cohort was used to validate brief delirium assessments using a psychiatrist's assessment as the reference standard.[5, 13] The local institutional review board approved these studies.

Setting and Participants

These studies were conducted in an urban emergency department located within an academic, tertiary care hospital with over 57,000 visits annually. Patients were included if they were 65 years or older and in the emergency department for <12 hours at the time of enrollment. The 12‐hour cutoff was used to include patients who presented to the emergency department in the evening and early morning hours. Patients were excluded if they were previously enrolled, non‐English speaking, comatose, or were nonverbal and unable to follow simple commands prior to the acute illness. Because the July 2009 to February 2012 cohort was designed to validate delirium assessments with auditory and visual components, patients were also excluded if they were deaf or blind.

Measurement of Arousal

RASS is an arousal scale commonly used in ICUs to assess depth of sedation and ranges from 5 (unarousable) to +4 (combative); 0 represents normal arousal.[10, 14] The RASS simply requires the rater to observe the patient during their routine interactions and does not require any additional cognitive testing. The RASS terms sedation was modified to drowsy (Table 1), because we wanted to capture impaired arousal regardless of sedation administration. We did not use the modified RASS (mRASS) proposed by the Veteran's Affairs Delirium Working Group, because it was published after data collection began.[1] The mRASS is very similar to the RASS, except it also incorporates a very informal inattention assessment. The RASS was ascertained by research assistants who were college students and graduates, and emergency medical technician basics and paramedics. The principal investigator gave them a 5‐minute didactic lecture about the RASS and observed them perform the RASS in at least 5 patients prior to the start of the study. Inter‐rater reliability between trained research assistants and a physician was assessed for 456 (42.0%) patients of the study sample. The weighted kappa of the RASS was 0.61, indicating very good inter‐rater reliability. Because the 81.7% of patients with impaired arousal had a RASS of 1, the RASS dichotomized as normal (RASS=0) or impaired (RASS other than 0).

Richmond Agitation‐Sedation Scale
ScoreTermDescription
  • NOTE: The Richmond Agitation‐Sedation Scale (RASS) is a brief (<10 seconds) arousal scale that was developed by Sessler et al.[10] The RASS is traditionally used in the intensive care unit to monitor depth of sedation. The terms were modified to better reflect the patient's level of arousal rather than sedation. A RASS of 0 indicates normal level of arousal (awake and alert), whereas a RASS <0 indicates decreased arousal, and a RASS >0 indicates increased arousal.

+4CombativeOvertly combative, violent, immediate danger to staff
+3Very agitatedPulls or removes tube(s) or catheter(s), aggressive
+2AgitatedFrequent nonpurposeful movement
+1RestlessAnxious but movements not aggressive or vigorous
0Alert and calm 
1Slight drowsyNot fully alert, but has sustained awakening (eye opening/eye contact) to voice (>10 seconds)
2Moderately drowsyBriefly awakens with eye contact to voice (<10 seconds)
3Very drowsyMovement or eye opening to voice (but no eye contact)
4Awakens to pain onlyNo response to voice, but movement or eye opening to physical stimulation
5UnarousableNo response to voice or physical stimulation

Death Ascertainment

Death within 6 months was ascertained using the following algorithm: (1) The electronic medical record was searched to determine the patient's death status. (2) Patients who had a documented emergency department visit, outpatient clinic visit, or hospitalization after 6 months were considered to be alive at 6 months. (3) For the remaining patients, date of death was searched in the Social Security Death Index (SSDI). (4) Patients without a death recorded in the SSDI 1 year after the index visit was considered to be alive at 6 months. Nine hundred thirty‐one (85.9%) out of 1084 patients had a recorded death in the medical record or SSDI, or had an emergency department or hospital visit documented in their record 6 months after the index visit.

Additional Variables Collected

Patients were considered to have dementia if they had: (1) documented dementia in the medical record, (2) a short form Informant Questionnaire on Cognitive Decline in the Elderly score (IQCODE) greater than 3.38,[15] or (3) prescribed cholinesterase inhibitors prior to admission. The short form IQCODE is an informant questionnaire with 16 items; a cutoff of 3.38 out of 5.00 is 79% sensitive and 82% specific for dementia.[16] Premorbid functional status was determined by the Katz Activities of Daily Living (Katz ADL) and ranges from 0 (completely dependent) to 6 (completely independent).[17] Patients with a score <5 were considered to be functionally dependent. Both the IQCODE and Katz ADL were prospectively collected in the emergency department at the time of enrollment.

The Charlson Comorbidity Index was used to measure comorbid burden.[18] The Acute Physiology Score (APS) of the Acute Physiology and Chronic Health Evaluation II score was used to quantify severity of illness.[19] The Glasgow Coma Scale was not included in the APS because it was not collected. Intravenous, intramuscular, and oral benzodiazepine and opioids given in the prehospital and emergency department were also recorded. The Charlson Comorbidity Index, APS, and benzodiazepine and opioid administration were collected after patient enrollment using the electronic medical record.

Within 3 hours of the RASS, a subset of 406 patients was evaluated by a consultation‐liaison psychiatrist who determined the patient's delirium status using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) criteria.[20] Details of their comprehensive assessments have been described in a previous report.[5]

Statistical Analysis

Measures of central tendency and dispersion for continuous variables were reported as medians and interquartile ranges. Categorical variables were reported as proportions. For simple comparisons, Wilcoxon rank sum tests were performed for continuous data, and 2 analyses or Fisher exact test were performed for categorical data. To evaluate the predictive validity of impaired arousal on 6‐month mortality, the cumulative probability of survival was estimated within 6 months from the study enrollment date using the Kaplan‐Meier method. Cox proportional hazards regression was performed to assess if impaired arousal was independently associated with 6‐month mortality after adjusting for age, gender, nonwhite race, comorbidity burden (Charlson Comorbidity Index), severity of illness (APS), dementia, functional dependence (Katz ADL <5), nursing home residence, admission status, and benzodiazepine or opioid medication administration. Patients were censored at the end of 6 months. The selection of covariates was based upon expert opinion and literature review. The number of covariates used for the model was limited by the number of events to minimize overfitting; 1 df was allowed for every 10 to 15 events.[21] Because severity of illness, psychoactive medication administration, and admission status might modify the relationship between 6‐month mortality and impaired arousal, 2‐way interaction terms were incorporated. To maintain parsimony and minimize overfitting and collinearity, nonsignificant interaction terms (P>0.20) were removed in the final model.[22] Hazard ratios (HR) with their 95% confidence interval (95% CI) were reported.

To determine if arousal was associated with 6‐month mortality in the absence of delirium, we performed another Cox proportional hazard regression in a subset of 406 patients who received a psychiatrist assessment. Six‐month mortality was the dependent variable, and the independent variable was a 3‐level categorical variable of different arousal/delirium combinations: (1) impaired arousal/delirium positive, (2) impaired arousal/delirium negative, and (3) normal arousal (with or without delirium). Because there were only 8 patients who had normal arousal with delirium, this group was collapsed into the normal arousal without delirium group. Because there were 55 deaths, the number of covariates that could be entered into the Cox proportional hazard regression model was limited. We used the inverse weighted propensity score method to help minimize residual confounding.[23] Traditional propensity score adjustment could not be performed because there were 3 arousal/delirium categories. Similar to propensity score adjustment, inverse weighted propensity score method was used to help balance the distribution of patient characteristics among the exposure groups and also allow adjustment for multiple confounders while minimizing the degrees of freedom expended. A propensity score was the probability of having a particular arousal/delirium category based upon baseline patient characteristics. Multinomial logistic regression was performed to calculate the propensity score, and the baseline covariates used were age, gender, nonwhite race, comorbidity burden, severity of illness, dementia, functional dependence, and nursing home residence. For the Cox proportional hazard regression model, each observation was weighted by the inverse of the propensity score for their given arousal/delirium category; propensity scores exceeding the 95th percentile were trimmed to avoid overly influential weighting. Benzodiazepine and opioid medications given in the emergency department and admission status were adjusted as covariates in the weighted Cox proportional hazard regression model.

Nineteen patients (1.8%) had missing Katz ADL; these missing values were imputed using multiple imputation. The reliability of the final regression models were internally validated using the bootstrap method.[21] Two thousand sets of bootstrap samples were generated by resampling the original data, and the optimism was estimated to determine the degree of overfitting.[21] An optimism value >0.85 indicated no evidence of substantial overfitting.[21] Variance inflation factors were used to check multicollinearity. Schoenfeld residuals were also analyzed to determine goodness‐of‐fit and assess for outliers. P values <0.05 were considered statistically significant. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC) and open source R statistical software version 3.0.1 (http://www.r‐project.org/).

RESULTS

A total of 1903 patients were screened, and 1084 patients met enrollment criteria (Figure 1). Of these, 1051 (97.0%) were non‐ICU patients. Patient characteristics of this cohort can be seen in Table 2. Enrolled patients and potentially eligible patients who presented to the emergency department during the enrollment window were similar in age, gender, and severity of illness, but enrolled patients were slightly more likely to have a chief complaint of chest pain and syncope (unpublished data).

Figure 1
Enrollment flow diagram. RASS, Richmond Agitation‐Sedation Scale. Patients who were non‐verbal or unable to follow simple commands prior to their acute illness were considered to have end‐stage dementia.
Patient Characteristics
VariablesNormal Arousal, n=835Impaired Arousal, n=249P Value
  • NOTE: Patient characteristics and demographics of enrolled patients. Continuous and ordinal variables are expressed in medians and interquartile (IQR) ranges. Categorical variables are expressed in absolute numbers and percentages. *Patient was considered to have dementia if it was documented in the medical record, the patient was on home cholineresterase inhibitors, or had a short‐form Informant Questionnaire on Cognitive Decline in the Elderly >3.38. Patients with a Katz Activities of Daily Living of <5 were considered to be functionally dependent. There were 19 patients with missing Katz Activities of Daily Living scores. Charlson index is a weighted scale used to measure comorbidity burden. Higher scores indicate higher comorbidity burden. The Acute Physiology Score (APS) of the Acute Physiology and Chronic Health Evaluation II score was used quantify severity of illness. Glasgow Coma Scale was not incorporated in this score. Higher scores indicate higher severity of illness.

Median age, y (IQR)74 (6980)75 (7083)0.005
Female gender459 (55.0%)132 (53.0%)0.586
Nonwhite race122 (14.6%)51 (20.5%)0.027
Residence  <0.001
Home752 (90.1%)204 (81.9%) 
Assisted living29 (3.5%)13 (5.2%) 
Rehabilitation8 (1.0%)5 (2.0%) 
Nursing home42 (5.0%)27 (10.8%) 
Dementia*175 (21.0%)119 (47.8%)<0.001
Dependent120 (14.4%)99 (39.8%)<0.001
Median Charlson (IQR)2 (1, 4)3 (2, 5)<0.001
Median APS (IQR)2 (1, 4)2 (1, 5)<0.001
Primary complaint  <0.001
Abdominal pain45 (5.4%)13 (5.2%) 
Altered mental status12 (1.4%)36 (14.5%) 
Chest pain128 (15.3%)31 (12.5%) 
Disturbances of sensation17 (2.0%)2 (0.8%) 
Dizziness16 (1.9%)2 (0.8%) 
Fever11 (1.3%)7 (2.8%) 
General illness, malaise26 (3.1%)5 (2.0%) 
General weakness68 (8.1%)29 (11.7%) 
Nausea/vomiting29 (3.5%)4 (1.6%) 
Shortness of breath85 (10.2%)21 (8.4%) 
Syncope46 (5.5%)10 (4.0%) 
Trauma, multiple organs19 (2.3%)8 (3.2%) 
Other333 (39.9%)81 (32.5%) 
Benzodiazepines or opioid medications administration188 (22.5%)67 (26.9%)0.152
Admitted to the hospital478 (57.3%)191 (76.7%)0.002
Internal medicine411 (86.0%)153 (80.1%) 
Surgery38 (8.0%)21 (11.0%) 
Neurology19 (4.0%)13 (6.8%) 
Psychiatry1 (0.2%)2 (1.1%) 
Unknown/missing9 (1.9%)2 (1.1%) 
Death within 6 months81 (9.7%)59 (23.7%)<0.001

Of those enrolled, 249 (23.0%) had an abnormal RASS at initial presentation, and their distribution can be seen in Figure 2. Within 6 months, patients with an abnormal RASS were more likely to die compared with patients with a RASS of 0 (23.7% vs 9.7%, P<0.001). The Kaplan‐Meier survival curves for all enrolled patients with impaired and normal RASS can be seen in Figure 3; the survival curve declined more slowly in patients with a normal RASS compared with those with an abnormal RASS.

Figure 2
Richmond Agitation‐Sedation Scale (RASS) distribution among enrolled patients. Distribution of RASS at initial presentation among 1084 acutely ill older patients, and of these, 1051 patients (97.0%) were non–intensive care unit patients. The RASS is a widely used arousal scale that can be performed during routine clinical care and takes <10 seconds to perform. A RASS of 0 indicates normal level of arousal (awake and alert), whereas a RASS of <0 indicates decreased arousal and a RASS of >0 indicates increased arousal.
Figure 3
Kaplan‐Meier survival curves in acutely ill older patients with a normal and impaired arousal at initial presentation over a 6‐month period. Arousal was assessed for using the Richmond Agitation‐Sedation Scale (RASS). Patients with impaired arousal were more likely to die compared to patients with normal arousal (23.7% vs 9.7%) within 6 months. Using Cox proportional hazard regression, patients with an abnormal RASS were 73% more likely to die within 6 months after adjusting for age, dementia, functional dependence, comorbidity burden, severity of illness, hearing impairment, nursing home residence, admission status, and administration of benzodiazepines/opioids medications. Severity of illness (P = 0.52), benzodiazepine/opioid medication administration (P = 0.38), and admission status (P = 0.57) did not modify the relationship between impaired arousal and 6‐month mortality. Abbreviations: CI, confidence interval.

Using Cox proportional hazards regression, the relationship between an abnormal RASS at initial presentation and 6‐month mortality persisted (HR: 1.73, 95% CI: 1.21‐2.49) after adjusting for age, sex, nonwhite race, comorbidity burden, severity of illness, dementia, functional dependence, nursing home residence, psychoactive medications given, and admission status. The interaction between an abnormal RASS and APS (severity of illness) had a P value of 0.52. The interaction between an abnormal RASS and benzodiazepine or opioid medication administration had a P value of 0.38. The interaction between an abnormal RASS and admission status had a P value of 0.57. This indicated that severity of illness, psychoactive medication administration, and admission status did not modify the relationship between an abnormal RASS and 6‐month mortality.

We analyzed a subset of 406 patients who received a psychiatrist's assessment to determine if an abnormal RASS was associated with 6‐month mortality regardless of delirium status using Cox proportional hazard regression weighted by the inverse of the propensity score. Patients with an abnormal RASS and no delirium were significantly associated with higher mortality compared to those with a normal RASS (HR: 2.20, 95% CI: 1.10‐4.41). Patients with an abnormal RASS with delirium also had an increased risk for 6‐month mortality (HR: 2.86, 95% CI: 1.29‐6.34).

All regression models were internally validated. There was no evidence of substantial overfitting or collinearity. The Schoenfeld residuals for each model were examined graphically and there was good model fit overall, and no significant outliers were observed.

DISCUSSION

Vital sign measurements are a fundamental component of patient care, and abnormalities can serve as an early warning signal of the patient's clinical deterioration. However, traditional vital signs do not include an assessment of the patient's brain function. Our chief finding is that impaired arousal at initial presentation, as determined by the nonphysician research staff, increased the risk of 6‐month mortality by 73% after adjusting for confounders in a diverse group of acutely ill older patients. This relationship existed regardless of severity of illness, administration of psychoactive medications, and admission status. Though impaired arousal is closely linked with delirium,[2, 24] which is another well‐known predictor of mortality,[11, 25, 26] the prognostic significance of impaired arousal appeared to extend beyond delirium. We observed that the relationship between 6‐month mortality and impaired arousal in the absence of delirium was remarkably similar to that observed with impaired arousal with delirium. Arousal can be assessed for by simply observing the patient during routine clinical care and can be performed by nonphysician and physician healthcare providers. Its assessment should be performed and communicated in conjunction with traditional vital sign measurements in the emergency department and inpatient settings.[1]

Most of the data linking impaired arousal to death have been collected in the ICU. Coma, which represents the most severe form of depressed arousal, has been shown to increase the likelihood of death regardless of underlying etiology.[27, 28, 29, 30, 31] This includes patients who have impaired arousal because they received sedative medications during mechanical ventilation.[32] Few studies have investigated the effect of impaired arousal in a non‐ICU patient population. Zuliani et al. observed that impaired arousal was associated with 30‐day mortality, but their study was conducted in 469 older stroke patients, limiting the study's external validity to a more general patient population.[33] Our data advance the current stage of knowledge; we observed a similar relationship between impaired arousal and 6‐month mortality in a much broader clinical population who were predominantly not critically ill regardless of delirium status. Additionally, most of our impaired arousal cohort had a RASS of 1, indicating that even subtle abnormalities portended adverse outcomes.

In addition to long‐term prognosis, the presence of impaired arousal has immediate clinical implications. Using arousal scales like the RASS can serve as a way for healthcare providers to succinctly communicate the patient's mental status in a standardized manner during transitions of care (eg, emergency physician to inpatient team). Regardless of which clinical setting they are in, older acutely ill patients with an impaired arousal may also require close monitoring, especially if the impairment is acute. Because of its close relationship with delirium, these patients likely have an underlying acute medical illness that precipitated their impaired arousal.

Understanding the true clinical significance of impaired arousal in the absence of delirium requires further study. Because of the fluctuating nature of delirium, it is possible that these patients may have initially been delirious and then became nondelirious during the psychiatrist's evaluation. Conversely, it is also possible that these patients may have eventually transitioned into delirium at later point in time; the presence of impaired arousal alone may be a precursor to delirium. Last, these patients may have had subsyndromal delirium, which is defined as having 1 or more delirium symptoms without ever meeting full DSM‐IV‐TR criteria for delirium.[34] Patients with subsyndromal delirium have poorer outcomes, such as prolonged hospitalizations, and higher mortality than patients without delirium symptoms.[34]

Additional studies are also needed to further clarify the impact of impaired arousal on nonmortality outcomes such as functional and cognitive decline. The prognostic significance of serial arousal measurements also requires further study. It is possible that patients whose impaired arousal rapidly resolves after an intervention may have better prognoses than those who have persistent impairment. The measurement of arousal may have additional clinical applications in disease prognosis models. The presence of altered mental status is incorporated in various disease‐specific risk scores such as the CURB‐65 or Pneumonia Severity Index for pneumonia,[35, 36] and the Pulmonary Embolism Severity Index for pulmonary embolism.[37] However, the definition of altered mental status is highly variable; it ranges from subjective impressions that can be unreliable to formal cognitive testing, which can be time consuming. Arousal scales such as the RASS may allow for more feasible, reliable, and standardized assessment of mental status. Future studies should investigate if incorporating the RASS would improve the discrimination of these disease‐severity indices.

This study has several notable limitations. We excluded patients with a RASS of 4 and 5, which represented comatose patients. This exclusion, however, likely biased our findings toward the null. We enrolled a convenience sample that may have introduced selection bias. However, our enrolled cohort was similar to all potentially eligible patients who presented to the emergency department during the study period. We also attempted to mitigate this selection bias by using multivariable regression and adjusting for factors that may have confounded the relationship between RASS and 6‐month mortality. This study was performed at a single, urban, academic hospital and enrolled patients who were aged 65 years and older. Our findings may not be generalizable to other settings and to those who are under 65 years of age. Because 406 patients received a psychiatric evaluation, this limited the number of covariates that could be incorporated into the multivariable model to evaluate if impaired arousal in the absence of delirium is associated with 6‐month mortality. To minimize residual confounding, we used the inverse weighted propensity score, but we acknowledge that this bias may still exist. Larger studies are needed to clarify the relationships between arousal, delirium, and mortality.

CONCLUSION

In conclusion, impaired arousal at initial presentation is an independent predictor for 6‐month mortality in a diverse group of acutely ill older patients, and this risk appears to be present even in the absence of delirium. Because of its ease of use and prognostic significance, it may be a useful vital sign for underlying brain dysfunction. Routine standardized assessment and communication of arousal during routine clinical care may be warranted.

Disclosures: Research reported in this publication was supported by the Vanderbilt Physician Scientist Development Award, Emergency Medicine Foundation, and National Institute on Aging of the National Institutes of Health under award number K23AG032355. This study was also supported by the National Center for Research Resources, grant UL1 RR024975‐01, and is now at the National Center for Advancing Translational Sciences, grant 2 UL1 TR000445‐06. Dr. Vasilevskis was supported in part by the National Institute on Aging of the National Institutes of Health under award number K23AG040157. Dr. Powers was supported by Health Resources and Services Administration Geriatric Education Centers, grant 1D31HP08823‐01‐00. Dr. Storrow was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K12HL1090 and the National Center for Advancing Translational Sciences under award number UL1TR000445. Dr. Ely was supported in part by the National Institute on Aging of the National Institutes of Health under award numbers R01AG027472 and R01AG035117, and a Veteran Affairs MERIT award. Drs. Vasilevskis, Schnelle, Dittus, Powers, and Ely were supported by the Veteran Affairs Geriatric Research, Education, and Clinical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of Vanderbilt University, Emergency Medicine Foundation, National Institutes of Health, and Veterans Affairs. The funding agencies did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

J.H.H., E.W.E., J.F.S., A.B.S., and R.D.S. conceived the trial. J.H.H., E.W.E., A.B.S., J.F.S., R.D.S., A.S., and A.W. participated in the study design. J.H.H. and A.W. recruited patients and collected the data. J.H.H., A.J.G., and A.S. analyzed the data. All authors participated in the interpretation of results. J.H.H. drafted the manuscript, and all authors contributed to the critical review and revision of the manuscript.

The authors report no conflicts of interest.

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  35. Lim WS, der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377382.
  36. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low‐risk patients with community‐acquired pneumonia. N Engl J Med. 1997;336:243250.
  37. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:10411046.
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Arousal is defined as the patient's overall level of responsiveness to the environment. Its assessment is standard of care in most intensive care units (ICUs) to monitor depth of sedation and underlying brain dysfunction. There has been recent interest in expanding the role of arousal assessment beyond the ICU. Specifically, the Veterans Affairs Delirium Working Group proposed that simple arousal assessment be a vital sign to quantify underlying brain dysfunction.[1] The rationale is that impaired arousal is closely linked with delirium,[2] and is an integral component of multiple delirium assessments.[3, 4, 5] Chester et al. observed that the presence of impaired arousal was 64% sensitive and 93% specific for delirium diagnosed by a psychiatrist.[2] Delirium is an under‐recognized public health problem that affects up to 25% of older hospitalized patients,[6, 7] is associated with a multitude of adverse outcomes such as death and accelerated cognitive decline,[8] and costs the US healthcare system an excess of $152 billion dollars.[9]

Most delirium assessments require the patient to undergo additional cognitive testing. The assessment of arousal, however, requires the rater to merely observe the patient during routine clinical care and can be easily integrated into the clinical workflow.[10] Because of its simplicity and brevity, assessing arousal alone using validated scales such as the Richmond Agitation‐Sedation Scale (RASS) may be a more appealing alternative to traditional, more complex delirium screening in the acute care setting. Its clinical utility would be further strengthened if impaired arousal was also associated with mortality, and conferred risk even in the absence of delirium. As a result, we sought to determine if impaired arousal at initial presentation in older acutely ill patients predicted 6‐month mortality and whether this relationship was present in the absence of delirium.

METHODS

Design Overview

We performed a planned secondary analysis of 2 prospective cohorts that enrolled patients from May 2007 to August 2008 between 8 am and 10 pm during the weekdays, and July 2009 to February 2012 between 8 am and 4 pm during the weekdays. The first cohort was designed to evaluate the relationship between delirium and patient outcomes.[11, 12] The second cohort was used to validate brief delirium assessments using a psychiatrist's assessment as the reference standard.[5, 13] The local institutional review board approved these studies.

Setting and Participants

These studies were conducted in an urban emergency department located within an academic, tertiary care hospital with over 57,000 visits annually. Patients were included if they were 65 years or older and in the emergency department for <12 hours at the time of enrollment. The 12‐hour cutoff was used to include patients who presented to the emergency department in the evening and early morning hours. Patients were excluded if they were previously enrolled, non‐English speaking, comatose, or were nonverbal and unable to follow simple commands prior to the acute illness. Because the July 2009 to February 2012 cohort was designed to validate delirium assessments with auditory and visual components, patients were also excluded if they were deaf or blind.

Measurement of Arousal

RASS is an arousal scale commonly used in ICUs to assess depth of sedation and ranges from 5 (unarousable) to +4 (combative); 0 represents normal arousal.[10, 14] The RASS simply requires the rater to observe the patient during their routine interactions and does not require any additional cognitive testing. The RASS terms sedation was modified to drowsy (Table 1), because we wanted to capture impaired arousal regardless of sedation administration. We did not use the modified RASS (mRASS) proposed by the Veteran's Affairs Delirium Working Group, because it was published after data collection began.[1] The mRASS is very similar to the RASS, except it also incorporates a very informal inattention assessment. The RASS was ascertained by research assistants who were college students and graduates, and emergency medical technician basics and paramedics. The principal investigator gave them a 5‐minute didactic lecture about the RASS and observed them perform the RASS in at least 5 patients prior to the start of the study. Inter‐rater reliability between trained research assistants and a physician was assessed for 456 (42.0%) patients of the study sample. The weighted kappa of the RASS was 0.61, indicating very good inter‐rater reliability. Because the 81.7% of patients with impaired arousal had a RASS of 1, the RASS dichotomized as normal (RASS=0) or impaired (RASS other than 0).

Richmond Agitation‐Sedation Scale
ScoreTermDescription
  • NOTE: The Richmond Agitation‐Sedation Scale (RASS) is a brief (<10 seconds) arousal scale that was developed by Sessler et al.[10] The RASS is traditionally used in the intensive care unit to monitor depth of sedation. The terms were modified to better reflect the patient's level of arousal rather than sedation. A RASS of 0 indicates normal level of arousal (awake and alert), whereas a RASS <0 indicates decreased arousal, and a RASS >0 indicates increased arousal.

+4CombativeOvertly combative, violent, immediate danger to staff
+3Very agitatedPulls or removes tube(s) or catheter(s), aggressive
+2AgitatedFrequent nonpurposeful movement
+1RestlessAnxious but movements not aggressive or vigorous
0Alert and calm 
1Slight drowsyNot fully alert, but has sustained awakening (eye opening/eye contact) to voice (>10 seconds)
2Moderately drowsyBriefly awakens with eye contact to voice (<10 seconds)
3Very drowsyMovement or eye opening to voice (but no eye contact)
4Awakens to pain onlyNo response to voice, but movement or eye opening to physical stimulation
5UnarousableNo response to voice or physical stimulation

Death Ascertainment

Death within 6 months was ascertained using the following algorithm: (1) The electronic medical record was searched to determine the patient's death status. (2) Patients who had a documented emergency department visit, outpatient clinic visit, or hospitalization after 6 months were considered to be alive at 6 months. (3) For the remaining patients, date of death was searched in the Social Security Death Index (SSDI). (4) Patients without a death recorded in the SSDI 1 year after the index visit was considered to be alive at 6 months. Nine hundred thirty‐one (85.9%) out of 1084 patients had a recorded death in the medical record or SSDI, or had an emergency department or hospital visit documented in their record 6 months after the index visit.

Additional Variables Collected

Patients were considered to have dementia if they had: (1) documented dementia in the medical record, (2) a short form Informant Questionnaire on Cognitive Decline in the Elderly score (IQCODE) greater than 3.38,[15] or (3) prescribed cholinesterase inhibitors prior to admission. The short form IQCODE is an informant questionnaire with 16 items; a cutoff of 3.38 out of 5.00 is 79% sensitive and 82% specific for dementia.[16] Premorbid functional status was determined by the Katz Activities of Daily Living (Katz ADL) and ranges from 0 (completely dependent) to 6 (completely independent).[17] Patients with a score <5 were considered to be functionally dependent. Both the IQCODE and Katz ADL were prospectively collected in the emergency department at the time of enrollment.

The Charlson Comorbidity Index was used to measure comorbid burden.[18] The Acute Physiology Score (APS) of the Acute Physiology and Chronic Health Evaluation II score was used to quantify severity of illness.[19] The Glasgow Coma Scale was not included in the APS because it was not collected. Intravenous, intramuscular, and oral benzodiazepine and opioids given in the prehospital and emergency department were also recorded. The Charlson Comorbidity Index, APS, and benzodiazepine and opioid administration were collected after patient enrollment using the electronic medical record.

Within 3 hours of the RASS, a subset of 406 patients was evaluated by a consultation‐liaison psychiatrist who determined the patient's delirium status using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) criteria.[20] Details of their comprehensive assessments have been described in a previous report.[5]

Statistical Analysis

Measures of central tendency and dispersion for continuous variables were reported as medians and interquartile ranges. Categorical variables were reported as proportions. For simple comparisons, Wilcoxon rank sum tests were performed for continuous data, and 2 analyses or Fisher exact test were performed for categorical data. To evaluate the predictive validity of impaired arousal on 6‐month mortality, the cumulative probability of survival was estimated within 6 months from the study enrollment date using the Kaplan‐Meier method. Cox proportional hazards regression was performed to assess if impaired arousal was independently associated with 6‐month mortality after adjusting for age, gender, nonwhite race, comorbidity burden (Charlson Comorbidity Index), severity of illness (APS), dementia, functional dependence (Katz ADL <5), nursing home residence, admission status, and benzodiazepine or opioid medication administration. Patients were censored at the end of 6 months. The selection of covariates was based upon expert opinion and literature review. The number of covariates used for the model was limited by the number of events to minimize overfitting; 1 df was allowed for every 10 to 15 events.[21] Because severity of illness, psychoactive medication administration, and admission status might modify the relationship between 6‐month mortality and impaired arousal, 2‐way interaction terms were incorporated. To maintain parsimony and minimize overfitting and collinearity, nonsignificant interaction terms (P>0.20) were removed in the final model.[22] Hazard ratios (HR) with their 95% confidence interval (95% CI) were reported.

To determine if arousal was associated with 6‐month mortality in the absence of delirium, we performed another Cox proportional hazard regression in a subset of 406 patients who received a psychiatrist assessment. Six‐month mortality was the dependent variable, and the independent variable was a 3‐level categorical variable of different arousal/delirium combinations: (1) impaired arousal/delirium positive, (2) impaired arousal/delirium negative, and (3) normal arousal (with or without delirium). Because there were only 8 patients who had normal arousal with delirium, this group was collapsed into the normal arousal without delirium group. Because there were 55 deaths, the number of covariates that could be entered into the Cox proportional hazard regression model was limited. We used the inverse weighted propensity score method to help minimize residual confounding.[23] Traditional propensity score adjustment could not be performed because there were 3 arousal/delirium categories. Similar to propensity score adjustment, inverse weighted propensity score method was used to help balance the distribution of patient characteristics among the exposure groups and also allow adjustment for multiple confounders while minimizing the degrees of freedom expended. A propensity score was the probability of having a particular arousal/delirium category based upon baseline patient characteristics. Multinomial logistic regression was performed to calculate the propensity score, and the baseline covariates used were age, gender, nonwhite race, comorbidity burden, severity of illness, dementia, functional dependence, and nursing home residence. For the Cox proportional hazard regression model, each observation was weighted by the inverse of the propensity score for their given arousal/delirium category; propensity scores exceeding the 95th percentile were trimmed to avoid overly influential weighting. Benzodiazepine and opioid medications given in the emergency department and admission status were adjusted as covariates in the weighted Cox proportional hazard regression model.

Nineteen patients (1.8%) had missing Katz ADL; these missing values were imputed using multiple imputation. The reliability of the final regression models were internally validated using the bootstrap method.[21] Two thousand sets of bootstrap samples were generated by resampling the original data, and the optimism was estimated to determine the degree of overfitting.[21] An optimism value >0.85 indicated no evidence of substantial overfitting.[21] Variance inflation factors were used to check multicollinearity. Schoenfeld residuals were also analyzed to determine goodness‐of‐fit and assess for outliers. P values <0.05 were considered statistically significant. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC) and open source R statistical software version 3.0.1 (http://www.r‐project.org/).

RESULTS

A total of 1903 patients were screened, and 1084 patients met enrollment criteria (Figure 1). Of these, 1051 (97.0%) were non‐ICU patients. Patient characteristics of this cohort can be seen in Table 2. Enrolled patients and potentially eligible patients who presented to the emergency department during the enrollment window were similar in age, gender, and severity of illness, but enrolled patients were slightly more likely to have a chief complaint of chest pain and syncope (unpublished data).

Figure 1
Enrollment flow diagram. RASS, Richmond Agitation‐Sedation Scale. Patients who were non‐verbal or unable to follow simple commands prior to their acute illness were considered to have end‐stage dementia.
Patient Characteristics
VariablesNormal Arousal, n=835Impaired Arousal, n=249P Value
  • NOTE: Patient characteristics and demographics of enrolled patients. Continuous and ordinal variables are expressed in medians and interquartile (IQR) ranges. Categorical variables are expressed in absolute numbers and percentages. *Patient was considered to have dementia if it was documented in the medical record, the patient was on home cholineresterase inhibitors, or had a short‐form Informant Questionnaire on Cognitive Decline in the Elderly >3.38. Patients with a Katz Activities of Daily Living of <5 were considered to be functionally dependent. There were 19 patients with missing Katz Activities of Daily Living scores. Charlson index is a weighted scale used to measure comorbidity burden. Higher scores indicate higher comorbidity burden. The Acute Physiology Score (APS) of the Acute Physiology and Chronic Health Evaluation II score was used quantify severity of illness. Glasgow Coma Scale was not incorporated in this score. Higher scores indicate higher severity of illness.

Median age, y (IQR)74 (6980)75 (7083)0.005
Female gender459 (55.0%)132 (53.0%)0.586
Nonwhite race122 (14.6%)51 (20.5%)0.027
Residence  <0.001
Home752 (90.1%)204 (81.9%) 
Assisted living29 (3.5%)13 (5.2%) 
Rehabilitation8 (1.0%)5 (2.0%) 
Nursing home42 (5.0%)27 (10.8%) 
Dementia*175 (21.0%)119 (47.8%)<0.001
Dependent120 (14.4%)99 (39.8%)<0.001
Median Charlson (IQR)2 (1, 4)3 (2, 5)<0.001
Median APS (IQR)2 (1, 4)2 (1, 5)<0.001
Primary complaint  <0.001
Abdominal pain45 (5.4%)13 (5.2%) 
Altered mental status12 (1.4%)36 (14.5%) 
Chest pain128 (15.3%)31 (12.5%) 
Disturbances of sensation17 (2.0%)2 (0.8%) 
Dizziness16 (1.9%)2 (0.8%) 
Fever11 (1.3%)7 (2.8%) 
General illness, malaise26 (3.1%)5 (2.0%) 
General weakness68 (8.1%)29 (11.7%) 
Nausea/vomiting29 (3.5%)4 (1.6%) 
Shortness of breath85 (10.2%)21 (8.4%) 
Syncope46 (5.5%)10 (4.0%) 
Trauma, multiple organs19 (2.3%)8 (3.2%) 
Other333 (39.9%)81 (32.5%) 
Benzodiazepines or opioid medications administration188 (22.5%)67 (26.9%)0.152
Admitted to the hospital478 (57.3%)191 (76.7%)0.002
Internal medicine411 (86.0%)153 (80.1%) 
Surgery38 (8.0%)21 (11.0%) 
Neurology19 (4.0%)13 (6.8%) 
Psychiatry1 (0.2%)2 (1.1%) 
Unknown/missing9 (1.9%)2 (1.1%) 
Death within 6 months81 (9.7%)59 (23.7%)<0.001

Of those enrolled, 249 (23.0%) had an abnormal RASS at initial presentation, and their distribution can be seen in Figure 2. Within 6 months, patients with an abnormal RASS were more likely to die compared with patients with a RASS of 0 (23.7% vs 9.7%, P<0.001). The Kaplan‐Meier survival curves for all enrolled patients with impaired and normal RASS can be seen in Figure 3; the survival curve declined more slowly in patients with a normal RASS compared with those with an abnormal RASS.

Figure 2
Richmond Agitation‐Sedation Scale (RASS) distribution among enrolled patients. Distribution of RASS at initial presentation among 1084 acutely ill older patients, and of these, 1051 patients (97.0%) were non–intensive care unit patients. The RASS is a widely used arousal scale that can be performed during routine clinical care and takes <10 seconds to perform. A RASS of 0 indicates normal level of arousal (awake and alert), whereas a RASS of <0 indicates decreased arousal and a RASS of >0 indicates increased arousal.
Figure 3
Kaplan‐Meier survival curves in acutely ill older patients with a normal and impaired arousal at initial presentation over a 6‐month period. Arousal was assessed for using the Richmond Agitation‐Sedation Scale (RASS). Patients with impaired arousal were more likely to die compared to patients with normal arousal (23.7% vs 9.7%) within 6 months. Using Cox proportional hazard regression, patients with an abnormal RASS were 73% more likely to die within 6 months after adjusting for age, dementia, functional dependence, comorbidity burden, severity of illness, hearing impairment, nursing home residence, admission status, and administration of benzodiazepines/opioids medications. Severity of illness (P = 0.52), benzodiazepine/opioid medication administration (P = 0.38), and admission status (P = 0.57) did not modify the relationship between impaired arousal and 6‐month mortality. Abbreviations: CI, confidence interval.

Using Cox proportional hazards regression, the relationship between an abnormal RASS at initial presentation and 6‐month mortality persisted (HR: 1.73, 95% CI: 1.21‐2.49) after adjusting for age, sex, nonwhite race, comorbidity burden, severity of illness, dementia, functional dependence, nursing home residence, psychoactive medications given, and admission status. The interaction between an abnormal RASS and APS (severity of illness) had a P value of 0.52. The interaction between an abnormal RASS and benzodiazepine or opioid medication administration had a P value of 0.38. The interaction between an abnormal RASS and admission status had a P value of 0.57. This indicated that severity of illness, psychoactive medication administration, and admission status did not modify the relationship between an abnormal RASS and 6‐month mortality.

We analyzed a subset of 406 patients who received a psychiatrist's assessment to determine if an abnormal RASS was associated with 6‐month mortality regardless of delirium status using Cox proportional hazard regression weighted by the inverse of the propensity score. Patients with an abnormal RASS and no delirium were significantly associated with higher mortality compared to those with a normal RASS (HR: 2.20, 95% CI: 1.10‐4.41). Patients with an abnormal RASS with delirium also had an increased risk for 6‐month mortality (HR: 2.86, 95% CI: 1.29‐6.34).

All regression models were internally validated. There was no evidence of substantial overfitting or collinearity. The Schoenfeld residuals for each model were examined graphically and there was good model fit overall, and no significant outliers were observed.

DISCUSSION

Vital sign measurements are a fundamental component of patient care, and abnormalities can serve as an early warning signal of the patient's clinical deterioration. However, traditional vital signs do not include an assessment of the patient's brain function. Our chief finding is that impaired arousal at initial presentation, as determined by the nonphysician research staff, increased the risk of 6‐month mortality by 73% after adjusting for confounders in a diverse group of acutely ill older patients. This relationship existed regardless of severity of illness, administration of psychoactive medications, and admission status. Though impaired arousal is closely linked with delirium,[2, 24] which is another well‐known predictor of mortality,[11, 25, 26] the prognostic significance of impaired arousal appeared to extend beyond delirium. We observed that the relationship between 6‐month mortality and impaired arousal in the absence of delirium was remarkably similar to that observed with impaired arousal with delirium. Arousal can be assessed for by simply observing the patient during routine clinical care and can be performed by nonphysician and physician healthcare providers. Its assessment should be performed and communicated in conjunction with traditional vital sign measurements in the emergency department and inpatient settings.[1]

Most of the data linking impaired arousal to death have been collected in the ICU. Coma, which represents the most severe form of depressed arousal, has been shown to increase the likelihood of death regardless of underlying etiology.[27, 28, 29, 30, 31] This includes patients who have impaired arousal because they received sedative medications during mechanical ventilation.[32] Few studies have investigated the effect of impaired arousal in a non‐ICU patient population. Zuliani et al. observed that impaired arousal was associated with 30‐day mortality, but their study was conducted in 469 older stroke patients, limiting the study's external validity to a more general patient population.[33] Our data advance the current stage of knowledge; we observed a similar relationship between impaired arousal and 6‐month mortality in a much broader clinical population who were predominantly not critically ill regardless of delirium status. Additionally, most of our impaired arousal cohort had a RASS of 1, indicating that even subtle abnormalities portended adverse outcomes.

In addition to long‐term prognosis, the presence of impaired arousal has immediate clinical implications. Using arousal scales like the RASS can serve as a way for healthcare providers to succinctly communicate the patient's mental status in a standardized manner during transitions of care (eg, emergency physician to inpatient team). Regardless of which clinical setting they are in, older acutely ill patients with an impaired arousal may also require close monitoring, especially if the impairment is acute. Because of its close relationship with delirium, these patients likely have an underlying acute medical illness that precipitated their impaired arousal.

Understanding the true clinical significance of impaired arousal in the absence of delirium requires further study. Because of the fluctuating nature of delirium, it is possible that these patients may have initially been delirious and then became nondelirious during the psychiatrist's evaluation. Conversely, it is also possible that these patients may have eventually transitioned into delirium at later point in time; the presence of impaired arousal alone may be a precursor to delirium. Last, these patients may have had subsyndromal delirium, which is defined as having 1 or more delirium symptoms without ever meeting full DSM‐IV‐TR criteria for delirium.[34] Patients with subsyndromal delirium have poorer outcomes, such as prolonged hospitalizations, and higher mortality than patients without delirium symptoms.[34]

Additional studies are also needed to further clarify the impact of impaired arousal on nonmortality outcomes such as functional and cognitive decline. The prognostic significance of serial arousal measurements also requires further study. It is possible that patients whose impaired arousal rapidly resolves after an intervention may have better prognoses than those who have persistent impairment. The measurement of arousal may have additional clinical applications in disease prognosis models. The presence of altered mental status is incorporated in various disease‐specific risk scores such as the CURB‐65 or Pneumonia Severity Index for pneumonia,[35, 36] and the Pulmonary Embolism Severity Index for pulmonary embolism.[37] However, the definition of altered mental status is highly variable; it ranges from subjective impressions that can be unreliable to formal cognitive testing, which can be time consuming. Arousal scales such as the RASS may allow for more feasible, reliable, and standardized assessment of mental status. Future studies should investigate if incorporating the RASS would improve the discrimination of these disease‐severity indices.

This study has several notable limitations. We excluded patients with a RASS of 4 and 5, which represented comatose patients. This exclusion, however, likely biased our findings toward the null. We enrolled a convenience sample that may have introduced selection bias. However, our enrolled cohort was similar to all potentially eligible patients who presented to the emergency department during the study period. We also attempted to mitigate this selection bias by using multivariable regression and adjusting for factors that may have confounded the relationship between RASS and 6‐month mortality. This study was performed at a single, urban, academic hospital and enrolled patients who were aged 65 years and older. Our findings may not be generalizable to other settings and to those who are under 65 years of age. Because 406 patients received a psychiatric evaluation, this limited the number of covariates that could be incorporated into the multivariable model to evaluate if impaired arousal in the absence of delirium is associated with 6‐month mortality. To minimize residual confounding, we used the inverse weighted propensity score, but we acknowledge that this bias may still exist. Larger studies are needed to clarify the relationships between arousal, delirium, and mortality.

CONCLUSION

In conclusion, impaired arousal at initial presentation is an independent predictor for 6‐month mortality in a diverse group of acutely ill older patients, and this risk appears to be present even in the absence of delirium. Because of its ease of use and prognostic significance, it may be a useful vital sign for underlying brain dysfunction. Routine standardized assessment and communication of arousal during routine clinical care may be warranted.

Disclosures: Research reported in this publication was supported by the Vanderbilt Physician Scientist Development Award, Emergency Medicine Foundation, and National Institute on Aging of the National Institutes of Health under award number K23AG032355. This study was also supported by the National Center for Research Resources, grant UL1 RR024975‐01, and is now at the National Center for Advancing Translational Sciences, grant 2 UL1 TR000445‐06. Dr. Vasilevskis was supported in part by the National Institute on Aging of the National Institutes of Health under award number K23AG040157. Dr. Powers was supported by Health Resources and Services Administration Geriatric Education Centers, grant 1D31HP08823‐01‐00. Dr. Storrow was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K12HL1090 and the National Center for Advancing Translational Sciences under award number UL1TR000445. Dr. Ely was supported in part by the National Institute on Aging of the National Institutes of Health under award numbers R01AG027472 and R01AG035117, and a Veteran Affairs MERIT award. Drs. Vasilevskis, Schnelle, Dittus, Powers, and Ely were supported by the Veteran Affairs Geriatric Research, Education, and Clinical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of Vanderbilt University, Emergency Medicine Foundation, National Institutes of Health, and Veterans Affairs. The funding agencies did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

J.H.H., E.W.E., J.F.S., A.B.S., and R.D.S. conceived the trial. J.H.H., E.W.E., A.B.S., J.F.S., R.D.S., A.S., and A.W. participated in the study design. J.H.H. and A.W. recruited patients and collected the data. J.H.H., A.J.G., and A.S. analyzed the data. All authors participated in the interpretation of results. J.H.H. drafted the manuscript, and all authors contributed to the critical review and revision of the manuscript.

The authors report no conflicts of interest.

Arousal is defined as the patient's overall level of responsiveness to the environment. Its assessment is standard of care in most intensive care units (ICUs) to monitor depth of sedation and underlying brain dysfunction. There has been recent interest in expanding the role of arousal assessment beyond the ICU. Specifically, the Veterans Affairs Delirium Working Group proposed that simple arousal assessment be a vital sign to quantify underlying brain dysfunction.[1] The rationale is that impaired arousal is closely linked with delirium,[2] and is an integral component of multiple delirium assessments.[3, 4, 5] Chester et al. observed that the presence of impaired arousal was 64% sensitive and 93% specific for delirium diagnosed by a psychiatrist.[2] Delirium is an under‐recognized public health problem that affects up to 25% of older hospitalized patients,[6, 7] is associated with a multitude of adverse outcomes such as death and accelerated cognitive decline,[8] and costs the US healthcare system an excess of $152 billion dollars.[9]

Most delirium assessments require the patient to undergo additional cognitive testing. The assessment of arousal, however, requires the rater to merely observe the patient during routine clinical care and can be easily integrated into the clinical workflow.[10] Because of its simplicity and brevity, assessing arousal alone using validated scales such as the Richmond Agitation‐Sedation Scale (RASS) may be a more appealing alternative to traditional, more complex delirium screening in the acute care setting. Its clinical utility would be further strengthened if impaired arousal was also associated with mortality, and conferred risk even in the absence of delirium. As a result, we sought to determine if impaired arousal at initial presentation in older acutely ill patients predicted 6‐month mortality and whether this relationship was present in the absence of delirium.

METHODS

Design Overview

We performed a planned secondary analysis of 2 prospective cohorts that enrolled patients from May 2007 to August 2008 between 8 am and 10 pm during the weekdays, and July 2009 to February 2012 between 8 am and 4 pm during the weekdays. The first cohort was designed to evaluate the relationship between delirium and patient outcomes.[11, 12] The second cohort was used to validate brief delirium assessments using a psychiatrist's assessment as the reference standard.[5, 13] The local institutional review board approved these studies.

Setting and Participants

These studies were conducted in an urban emergency department located within an academic, tertiary care hospital with over 57,000 visits annually. Patients were included if they were 65 years or older and in the emergency department for <12 hours at the time of enrollment. The 12‐hour cutoff was used to include patients who presented to the emergency department in the evening and early morning hours. Patients were excluded if they were previously enrolled, non‐English speaking, comatose, or were nonverbal and unable to follow simple commands prior to the acute illness. Because the July 2009 to February 2012 cohort was designed to validate delirium assessments with auditory and visual components, patients were also excluded if they were deaf or blind.

Measurement of Arousal

RASS is an arousal scale commonly used in ICUs to assess depth of sedation and ranges from 5 (unarousable) to +4 (combative); 0 represents normal arousal.[10, 14] The RASS simply requires the rater to observe the patient during their routine interactions and does not require any additional cognitive testing. The RASS terms sedation was modified to drowsy (Table 1), because we wanted to capture impaired arousal regardless of sedation administration. We did not use the modified RASS (mRASS) proposed by the Veteran's Affairs Delirium Working Group, because it was published after data collection began.[1] The mRASS is very similar to the RASS, except it also incorporates a very informal inattention assessment. The RASS was ascertained by research assistants who were college students and graduates, and emergency medical technician basics and paramedics. The principal investigator gave them a 5‐minute didactic lecture about the RASS and observed them perform the RASS in at least 5 patients prior to the start of the study. Inter‐rater reliability between trained research assistants and a physician was assessed for 456 (42.0%) patients of the study sample. The weighted kappa of the RASS was 0.61, indicating very good inter‐rater reliability. Because the 81.7% of patients with impaired arousal had a RASS of 1, the RASS dichotomized as normal (RASS=0) or impaired (RASS other than 0).

Richmond Agitation‐Sedation Scale
ScoreTermDescription
  • NOTE: The Richmond Agitation‐Sedation Scale (RASS) is a brief (<10 seconds) arousal scale that was developed by Sessler et al.[10] The RASS is traditionally used in the intensive care unit to monitor depth of sedation. The terms were modified to better reflect the patient's level of arousal rather than sedation. A RASS of 0 indicates normal level of arousal (awake and alert), whereas a RASS <0 indicates decreased arousal, and a RASS >0 indicates increased arousal.

+4CombativeOvertly combative, violent, immediate danger to staff
+3Very agitatedPulls or removes tube(s) or catheter(s), aggressive
+2AgitatedFrequent nonpurposeful movement
+1RestlessAnxious but movements not aggressive or vigorous
0Alert and calm 
1Slight drowsyNot fully alert, but has sustained awakening (eye opening/eye contact) to voice (>10 seconds)
2Moderately drowsyBriefly awakens with eye contact to voice (<10 seconds)
3Very drowsyMovement or eye opening to voice (but no eye contact)
4Awakens to pain onlyNo response to voice, but movement or eye opening to physical stimulation
5UnarousableNo response to voice or physical stimulation

Death Ascertainment

Death within 6 months was ascertained using the following algorithm: (1) The electronic medical record was searched to determine the patient's death status. (2) Patients who had a documented emergency department visit, outpatient clinic visit, or hospitalization after 6 months were considered to be alive at 6 months. (3) For the remaining patients, date of death was searched in the Social Security Death Index (SSDI). (4) Patients without a death recorded in the SSDI 1 year after the index visit was considered to be alive at 6 months. Nine hundred thirty‐one (85.9%) out of 1084 patients had a recorded death in the medical record or SSDI, or had an emergency department or hospital visit documented in their record 6 months after the index visit.

Additional Variables Collected

Patients were considered to have dementia if they had: (1) documented dementia in the medical record, (2) a short form Informant Questionnaire on Cognitive Decline in the Elderly score (IQCODE) greater than 3.38,[15] or (3) prescribed cholinesterase inhibitors prior to admission. The short form IQCODE is an informant questionnaire with 16 items; a cutoff of 3.38 out of 5.00 is 79% sensitive and 82% specific for dementia.[16] Premorbid functional status was determined by the Katz Activities of Daily Living (Katz ADL) and ranges from 0 (completely dependent) to 6 (completely independent).[17] Patients with a score <5 were considered to be functionally dependent. Both the IQCODE and Katz ADL were prospectively collected in the emergency department at the time of enrollment.

The Charlson Comorbidity Index was used to measure comorbid burden.[18] The Acute Physiology Score (APS) of the Acute Physiology and Chronic Health Evaluation II score was used to quantify severity of illness.[19] The Glasgow Coma Scale was not included in the APS because it was not collected. Intravenous, intramuscular, and oral benzodiazepine and opioids given in the prehospital and emergency department were also recorded. The Charlson Comorbidity Index, APS, and benzodiazepine and opioid administration were collected after patient enrollment using the electronic medical record.

Within 3 hours of the RASS, a subset of 406 patients was evaluated by a consultation‐liaison psychiatrist who determined the patient's delirium status using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) criteria.[20] Details of their comprehensive assessments have been described in a previous report.[5]

Statistical Analysis

Measures of central tendency and dispersion for continuous variables were reported as medians and interquartile ranges. Categorical variables were reported as proportions. For simple comparisons, Wilcoxon rank sum tests were performed for continuous data, and 2 analyses or Fisher exact test were performed for categorical data. To evaluate the predictive validity of impaired arousal on 6‐month mortality, the cumulative probability of survival was estimated within 6 months from the study enrollment date using the Kaplan‐Meier method. Cox proportional hazards regression was performed to assess if impaired arousal was independently associated with 6‐month mortality after adjusting for age, gender, nonwhite race, comorbidity burden (Charlson Comorbidity Index), severity of illness (APS), dementia, functional dependence (Katz ADL <5), nursing home residence, admission status, and benzodiazepine or opioid medication administration. Patients were censored at the end of 6 months. The selection of covariates was based upon expert opinion and literature review. The number of covariates used for the model was limited by the number of events to minimize overfitting; 1 df was allowed for every 10 to 15 events.[21] Because severity of illness, psychoactive medication administration, and admission status might modify the relationship between 6‐month mortality and impaired arousal, 2‐way interaction terms were incorporated. To maintain parsimony and minimize overfitting and collinearity, nonsignificant interaction terms (P>0.20) were removed in the final model.[22] Hazard ratios (HR) with their 95% confidence interval (95% CI) were reported.

To determine if arousal was associated with 6‐month mortality in the absence of delirium, we performed another Cox proportional hazard regression in a subset of 406 patients who received a psychiatrist assessment. Six‐month mortality was the dependent variable, and the independent variable was a 3‐level categorical variable of different arousal/delirium combinations: (1) impaired arousal/delirium positive, (2) impaired arousal/delirium negative, and (3) normal arousal (with or without delirium). Because there were only 8 patients who had normal arousal with delirium, this group was collapsed into the normal arousal without delirium group. Because there were 55 deaths, the number of covariates that could be entered into the Cox proportional hazard regression model was limited. We used the inverse weighted propensity score method to help minimize residual confounding.[23] Traditional propensity score adjustment could not be performed because there were 3 arousal/delirium categories. Similar to propensity score adjustment, inverse weighted propensity score method was used to help balance the distribution of patient characteristics among the exposure groups and also allow adjustment for multiple confounders while minimizing the degrees of freedom expended. A propensity score was the probability of having a particular arousal/delirium category based upon baseline patient characteristics. Multinomial logistic regression was performed to calculate the propensity score, and the baseline covariates used were age, gender, nonwhite race, comorbidity burden, severity of illness, dementia, functional dependence, and nursing home residence. For the Cox proportional hazard regression model, each observation was weighted by the inverse of the propensity score for their given arousal/delirium category; propensity scores exceeding the 95th percentile were trimmed to avoid overly influential weighting. Benzodiazepine and opioid medications given in the emergency department and admission status were adjusted as covariates in the weighted Cox proportional hazard regression model.

Nineteen patients (1.8%) had missing Katz ADL; these missing values were imputed using multiple imputation. The reliability of the final regression models were internally validated using the bootstrap method.[21] Two thousand sets of bootstrap samples were generated by resampling the original data, and the optimism was estimated to determine the degree of overfitting.[21] An optimism value >0.85 indicated no evidence of substantial overfitting.[21] Variance inflation factors were used to check multicollinearity. Schoenfeld residuals were also analyzed to determine goodness‐of‐fit and assess for outliers. P values <0.05 were considered statistically significant. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC) and open source R statistical software version 3.0.1 (http://www.r‐project.org/).

RESULTS

A total of 1903 patients were screened, and 1084 patients met enrollment criteria (Figure 1). Of these, 1051 (97.0%) were non‐ICU patients. Patient characteristics of this cohort can be seen in Table 2. Enrolled patients and potentially eligible patients who presented to the emergency department during the enrollment window were similar in age, gender, and severity of illness, but enrolled patients were slightly more likely to have a chief complaint of chest pain and syncope (unpublished data).

Figure 1
Enrollment flow diagram. RASS, Richmond Agitation‐Sedation Scale. Patients who were non‐verbal or unable to follow simple commands prior to their acute illness were considered to have end‐stage dementia.
Patient Characteristics
VariablesNormal Arousal, n=835Impaired Arousal, n=249P Value
  • NOTE: Patient characteristics and demographics of enrolled patients. Continuous and ordinal variables are expressed in medians and interquartile (IQR) ranges. Categorical variables are expressed in absolute numbers and percentages. *Patient was considered to have dementia if it was documented in the medical record, the patient was on home cholineresterase inhibitors, or had a short‐form Informant Questionnaire on Cognitive Decline in the Elderly >3.38. Patients with a Katz Activities of Daily Living of <5 were considered to be functionally dependent. There were 19 patients with missing Katz Activities of Daily Living scores. Charlson index is a weighted scale used to measure comorbidity burden. Higher scores indicate higher comorbidity burden. The Acute Physiology Score (APS) of the Acute Physiology and Chronic Health Evaluation II score was used quantify severity of illness. Glasgow Coma Scale was not incorporated in this score. Higher scores indicate higher severity of illness.

Median age, y (IQR)74 (6980)75 (7083)0.005
Female gender459 (55.0%)132 (53.0%)0.586
Nonwhite race122 (14.6%)51 (20.5%)0.027
Residence  <0.001
Home752 (90.1%)204 (81.9%) 
Assisted living29 (3.5%)13 (5.2%) 
Rehabilitation8 (1.0%)5 (2.0%) 
Nursing home42 (5.0%)27 (10.8%) 
Dementia*175 (21.0%)119 (47.8%)<0.001
Dependent120 (14.4%)99 (39.8%)<0.001
Median Charlson (IQR)2 (1, 4)3 (2, 5)<0.001
Median APS (IQR)2 (1, 4)2 (1, 5)<0.001
Primary complaint  <0.001
Abdominal pain45 (5.4%)13 (5.2%) 
Altered mental status12 (1.4%)36 (14.5%) 
Chest pain128 (15.3%)31 (12.5%) 
Disturbances of sensation17 (2.0%)2 (0.8%) 
Dizziness16 (1.9%)2 (0.8%) 
Fever11 (1.3%)7 (2.8%) 
General illness, malaise26 (3.1%)5 (2.0%) 
General weakness68 (8.1%)29 (11.7%) 
Nausea/vomiting29 (3.5%)4 (1.6%) 
Shortness of breath85 (10.2%)21 (8.4%) 
Syncope46 (5.5%)10 (4.0%) 
Trauma, multiple organs19 (2.3%)8 (3.2%) 
Other333 (39.9%)81 (32.5%) 
Benzodiazepines or opioid medications administration188 (22.5%)67 (26.9%)0.152
Admitted to the hospital478 (57.3%)191 (76.7%)0.002
Internal medicine411 (86.0%)153 (80.1%) 
Surgery38 (8.0%)21 (11.0%) 
Neurology19 (4.0%)13 (6.8%) 
Psychiatry1 (0.2%)2 (1.1%) 
Unknown/missing9 (1.9%)2 (1.1%) 
Death within 6 months81 (9.7%)59 (23.7%)<0.001

Of those enrolled, 249 (23.0%) had an abnormal RASS at initial presentation, and their distribution can be seen in Figure 2. Within 6 months, patients with an abnormal RASS were more likely to die compared with patients with a RASS of 0 (23.7% vs 9.7%, P<0.001). The Kaplan‐Meier survival curves for all enrolled patients with impaired and normal RASS can be seen in Figure 3; the survival curve declined more slowly in patients with a normal RASS compared with those with an abnormal RASS.

Figure 2
Richmond Agitation‐Sedation Scale (RASS) distribution among enrolled patients. Distribution of RASS at initial presentation among 1084 acutely ill older patients, and of these, 1051 patients (97.0%) were non–intensive care unit patients. The RASS is a widely used arousal scale that can be performed during routine clinical care and takes <10 seconds to perform. A RASS of 0 indicates normal level of arousal (awake and alert), whereas a RASS of <0 indicates decreased arousal and a RASS of >0 indicates increased arousal.
Figure 3
Kaplan‐Meier survival curves in acutely ill older patients with a normal and impaired arousal at initial presentation over a 6‐month period. Arousal was assessed for using the Richmond Agitation‐Sedation Scale (RASS). Patients with impaired arousal were more likely to die compared to patients with normal arousal (23.7% vs 9.7%) within 6 months. Using Cox proportional hazard regression, patients with an abnormal RASS were 73% more likely to die within 6 months after adjusting for age, dementia, functional dependence, comorbidity burden, severity of illness, hearing impairment, nursing home residence, admission status, and administration of benzodiazepines/opioids medications. Severity of illness (P = 0.52), benzodiazepine/opioid medication administration (P = 0.38), and admission status (P = 0.57) did not modify the relationship between impaired arousal and 6‐month mortality. Abbreviations: CI, confidence interval.

Using Cox proportional hazards regression, the relationship between an abnormal RASS at initial presentation and 6‐month mortality persisted (HR: 1.73, 95% CI: 1.21‐2.49) after adjusting for age, sex, nonwhite race, comorbidity burden, severity of illness, dementia, functional dependence, nursing home residence, psychoactive medications given, and admission status. The interaction between an abnormal RASS and APS (severity of illness) had a P value of 0.52. The interaction between an abnormal RASS and benzodiazepine or opioid medication administration had a P value of 0.38. The interaction between an abnormal RASS and admission status had a P value of 0.57. This indicated that severity of illness, psychoactive medication administration, and admission status did not modify the relationship between an abnormal RASS and 6‐month mortality.

We analyzed a subset of 406 patients who received a psychiatrist's assessment to determine if an abnormal RASS was associated with 6‐month mortality regardless of delirium status using Cox proportional hazard regression weighted by the inverse of the propensity score. Patients with an abnormal RASS and no delirium were significantly associated with higher mortality compared to those with a normal RASS (HR: 2.20, 95% CI: 1.10‐4.41). Patients with an abnormal RASS with delirium also had an increased risk for 6‐month mortality (HR: 2.86, 95% CI: 1.29‐6.34).

All regression models were internally validated. There was no evidence of substantial overfitting or collinearity. The Schoenfeld residuals for each model were examined graphically and there was good model fit overall, and no significant outliers were observed.

DISCUSSION

Vital sign measurements are a fundamental component of patient care, and abnormalities can serve as an early warning signal of the patient's clinical deterioration. However, traditional vital signs do not include an assessment of the patient's brain function. Our chief finding is that impaired arousal at initial presentation, as determined by the nonphysician research staff, increased the risk of 6‐month mortality by 73% after adjusting for confounders in a diverse group of acutely ill older patients. This relationship existed regardless of severity of illness, administration of psychoactive medications, and admission status. Though impaired arousal is closely linked with delirium,[2, 24] which is another well‐known predictor of mortality,[11, 25, 26] the prognostic significance of impaired arousal appeared to extend beyond delirium. We observed that the relationship between 6‐month mortality and impaired arousal in the absence of delirium was remarkably similar to that observed with impaired arousal with delirium. Arousal can be assessed for by simply observing the patient during routine clinical care and can be performed by nonphysician and physician healthcare providers. Its assessment should be performed and communicated in conjunction with traditional vital sign measurements in the emergency department and inpatient settings.[1]

Most of the data linking impaired arousal to death have been collected in the ICU. Coma, which represents the most severe form of depressed arousal, has been shown to increase the likelihood of death regardless of underlying etiology.[27, 28, 29, 30, 31] This includes patients who have impaired arousal because they received sedative medications during mechanical ventilation.[32] Few studies have investigated the effect of impaired arousal in a non‐ICU patient population. Zuliani et al. observed that impaired arousal was associated with 30‐day mortality, but their study was conducted in 469 older stroke patients, limiting the study's external validity to a more general patient population.[33] Our data advance the current stage of knowledge; we observed a similar relationship between impaired arousal and 6‐month mortality in a much broader clinical population who were predominantly not critically ill regardless of delirium status. Additionally, most of our impaired arousal cohort had a RASS of 1, indicating that even subtle abnormalities portended adverse outcomes.

In addition to long‐term prognosis, the presence of impaired arousal has immediate clinical implications. Using arousal scales like the RASS can serve as a way for healthcare providers to succinctly communicate the patient's mental status in a standardized manner during transitions of care (eg, emergency physician to inpatient team). Regardless of which clinical setting they are in, older acutely ill patients with an impaired arousal may also require close monitoring, especially if the impairment is acute. Because of its close relationship with delirium, these patients likely have an underlying acute medical illness that precipitated their impaired arousal.

Understanding the true clinical significance of impaired arousal in the absence of delirium requires further study. Because of the fluctuating nature of delirium, it is possible that these patients may have initially been delirious and then became nondelirious during the psychiatrist's evaluation. Conversely, it is also possible that these patients may have eventually transitioned into delirium at later point in time; the presence of impaired arousal alone may be a precursor to delirium. Last, these patients may have had subsyndromal delirium, which is defined as having 1 or more delirium symptoms without ever meeting full DSM‐IV‐TR criteria for delirium.[34] Patients with subsyndromal delirium have poorer outcomes, such as prolonged hospitalizations, and higher mortality than patients without delirium symptoms.[34]

Additional studies are also needed to further clarify the impact of impaired arousal on nonmortality outcomes such as functional and cognitive decline. The prognostic significance of serial arousal measurements also requires further study. It is possible that patients whose impaired arousal rapidly resolves after an intervention may have better prognoses than those who have persistent impairment. The measurement of arousal may have additional clinical applications in disease prognosis models. The presence of altered mental status is incorporated in various disease‐specific risk scores such as the CURB‐65 or Pneumonia Severity Index for pneumonia,[35, 36] and the Pulmonary Embolism Severity Index for pulmonary embolism.[37] However, the definition of altered mental status is highly variable; it ranges from subjective impressions that can be unreliable to formal cognitive testing, which can be time consuming. Arousal scales such as the RASS may allow for more feasible, reliable, and standardized assessment of mental status. Future studies should investigate if incorporating the RASS would improve the discrimination of these disease‐severity indices.

This study has several notable limitations. We excluded patients with a RASS of 4 and 5, which represented comatose patients. This exclusion, however, likely biased our findings toward the null. We enrolled a convenience sample that may have introduced selection bias. However, our enrolled cohort was similar to all potentially eligible patients who presented to the emergency department during the study period. We also attempted to mitigate this selection bias by using multivariable regression and adjusting for factors that may have confounded the relationship between RASS and 6‐month mortality. This study was performed at a single, urban, academic hospital and enrolled patients who were aged 65 years and older. Our findings may not be generalizable to other settings and to those who are under 65 years of age. Because 406 patients received a psychiatric evaluation, this limited the number of covariates that could be incorporated into the multivariable model to evaluate if impaired arousal in the absence of delirium is associated with 6‐month mortality. To minimize residual confounding, we used the inverse weighted propensity score, but we acknowledge that this bias may still exist. Larger studies are needed to clarify the relationships between arousal, delirium, and mortality.

CONCLUSION

In conclusion, impaired arousal at initial presentation is an independent predictor for 6‐month mortality in a diverse group of acutely ill older patients, and this risk appears to be present even in the absence of delirium. Because of its ease of use and prognostic significance, it may be a useful vital sign for underlying brain dysfunction. Routine standardized assessment and communication of arousal during routine clinical care may be warranted.

Disclosures: Research reported in this publication was supported by the Vanderbilt Physician Scientist Development Award, Emergency Medicine Foundation, and National Institute on Aging of the National Institutes of Health under award number K23AG032355. This study was also supported by the National Center for Research Resources, grant UL1 RR024975‐01, and is now at the National Center for Advancing Translational Sciences, grant 2 UL1 TR000445‐06. Dr. Vasilevskis was supported in part by the National Institute on Aging of the National Institutes of Health under award number K23AG040157. Dr. Powers was supported by Health Resources and Services Administration Geriatric Education Centers, grant 1D31HP08823‐01‐00. Dr. Storrow was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K12HL1090 and the National Center for Advancing Translational Sciences under award number UL1TR000445. Dr. Ely was supported in part by the National Institute on Aging of the National Institutes of Health under award numbers R01AG027472 and R01AG035117, and a Veteran Affairs MERIT award. Drs. Vasilevskis, Schnelle, Dittus, Powers, and Ely were supported by the Veteran Affairs Geriatric Research, Education, and Clinical Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of Vanderbilt University, Emergency Medicine Foundation, National Institutes of Health, and Veterans Affairs. The funding agencies did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

J.H.H., E.W.E., J.F.S., A.B.S., and R.D.S. conceived the trial. J.H.H., E.W.E., A.B.S., J.F.S., R.D.S., A.S., and A.W. participated in the study design. J.H.H. and A.W. recruited patients and collected the data. J.H.H., A.J.G., and A.S. analyzed the data. All authors participated in the interpretation of results. J.H.H. drafted the manuscript, and all authors contributed to the critical review and revision of the manuscript.

The authors report no conflicts of interest.

References
  1. Flaherty JH, Shay K, Weir C, et al. The development of a mental status vital sign for use across the spectrum of care. J Am Med Dir Assoc. 2009;10:379380.
  2. Chester JG, Beth Harrington M, Rudolph JL, Group VADW. Serial administration of a modified Richmond Agitation and Sedation Scale for delirium screening. J Hosp Med. 2012;7:450453.
  3. Inouye SK, Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113:941948.
  4. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM‐ICU). JAMA. 2001;286:27032710.
  5. Han JH, Wilson A, Vasilevskis EE, et al. Diagnosing delirium in older emergency department patients: validity and reliability of the Delirium Triage Screen And The Brief Confusion Assessment Method. Ann Emerg Med. 2013;62:457465.
  6. Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three‐site epidemiologic study. J Gen Intern Med. 1998;13:234242.
  7. Pitkala KH, Laurila JV, Strandberg TE, Tilvis RS. Prognostic significance of delirium in frail older people. Dement Geriatr Cogn Disord. 2005;19:158163.
  8. Witlox J, Eurelings LS, Jonghe JF, Kalisvaart KJ, Eikelenboom P, Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. JAMA. 2010;304:443451.
  9. Leslie DL, Marcantonio ER, Zhang Y, Leo‐Summers L, Inouye SK. One‐year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168:2732.
  10. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation‐Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166:13381344.
  11. Han JH, Shintani A, Eden S, et al. Delirium in the emergency department: an independent predictor of death within 6 months. Ann Emerg Med. 2010;56:244252.
  12. Han JH, Eden S, Shintani A, et al. Delirium in older emergency department patients is an independent predictor of hospital length of stay. Acad Emerg Med. 2011;18:451457.
  13. Han JH, Wilson A, Graves AJ, et al. Validation of the Confusion Assessment Method For The Intensive Care Unit in older emergency department patients. Acad Emerg Med. 2014;21:180187.
  14. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation‐Sedation Scale (RASS). JAMA. 2003;289:29832991.
  15. Holsinger T, Deveau J, Boustani M, Williams JW. Does this patient have dementia? JAMA. 2007;297:23912404.
  16. Jorm AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross‐validation. Psychol Med. 1994;24:145153.
  17. Katz S. Assessing self‐maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31:721727.
  18. Murray SB, Bates DW, Ngo L, Ufberg JW, Shapiro NI. Charlson Index is associated with one‐year mortality in emergency department patients with suspected infection. Acad Emerg Med. 2006;13:530536.
  19. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818829.
  20. American Psychiatric Association. Task Force on DSM‐IV. Diagnostic and Statistical Manual of Mental Disorders: DSM‐IV‐TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.
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  23. Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46:399424.
  24. Meagher DJ, Maclullich AM, Laurila JV. Defining delirium for the International Classification of Diseases, 11th Revision. J Psychosom Res. 2008;65:207214.
  25. McCusker J, Cole M, Abrahamowicz M, Primeau F, Belzile E. Delirium predicts 12‐month mortality. Arch Intern Med. 2002;162:457463.
  26. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291:17531762.
  27. Teres D, Brown RB, Lemeshow S. Predicting mortality of intensive care unit patients. The importance of coma. Crit Care Med. 1982;10:8695.
  28. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;1:480484.
  29. Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic‐ischemic coma. JAMA. 1985;253:14201426.
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  31. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291:870879.
  32. Shehabi Y, Bellomo R, Reade MC, et al. Early intensive care sedation predicts long‐term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186:724731.
  33. Zuliani G, Cherubini A, Ranzini M, Ruggiero C, Atti AR, Fellin R. Risk factors for short‐term mortality in older subjects with acute ischemic stroke. Gerontology. 2006;52:231236.
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  36. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low‐risk patients with community‐acquired pneumonia. N Engl J Med. 1997;336:243250.
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References
  1. Flaherty JH, Shay K, Weir C, et al. The development of a mental status vital sign for use across the spectrum of care. J Am Med Dir Assoc. 2009;10:379380.
  2. Chester JG, Beth Harrington M, Rudolph JL, Group VADW. Serial administration of a modified Richmond Agitation and Sedation Scale for delirium screening. J Hosp Med. 2012;7:450453.
  3. Inouye SK, Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113:941948.
  4. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM‐ICU). JAMA. 2001;286:27032710.
  5. Han JH, Wilson A, Vasilevskis EE, et al. Diagnosing delirium in older emergency department patients: validity and reliability of the Delirium Triage Screen And The Brief Confusion Assessment Method. Ann Emerg Med. 2013;62:457465.
  6. Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three‐site epidemiologic study. J Gen Intern Med. 1998;13:234242.
  7. Pitkala KH, Laurila JV, Strandberg TE, Tilvis RS. Prognostic significance of delirium in frail older people. Dement Geriatr Cogn Disord. 2005;19:158163.
  8. Witlox J, Eurelings LS, Jonghe JF, Kalisvaart KJ, Eikelenboom P, Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. JAMA. 2010;304:443451.
  9. Leslie DL, Marcantonio ER, Zhang Y, Leo‐Summers L, Inouye SK. One‐year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168:2732.
  10. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation‐Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166:13381344.
  11. Han JH, Shintani A, Eden S, et al. Delirium in the emergency department: an independent predictor of death within 6 months. Ann Emerg Med. 2010;56:244252.
  12. Han JH, Eden S, Shintani A, et al. Delirium in older emergency department patients is an independent predictor of hospital length of stay. Acad Emerg Med. 2011;18:451457.
  13. Han JH, Wilson A, Graves AJ, et al. Validation of the Confusion Assessment Method For The Intensive Care Unit in older emergency department patients. Acad Emerg Med. 2014;21:180187.
  14. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation‐Sedation Scale (RASS). JAMA. 2003;289:29832991.
  15. Holsinger T, Deveau J, Boustani M, Williams JW. Does this patient have dementia? JAMA. 2007;297:23912404.
  16. Jorm AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross‐validation. Psychol Med. 1994;24:145153.
  17. Katz S. Assessing self‐maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31:721727.
  18. Murray SB, Bates DW, Ngo L, Ufberg JW, Shapiro NI. Charlson Index is associated with one‐year mortality in emergency department patients with suspected infection. Acad Emerg Med. 2006;13:530536.
  19. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818829.
  20. American Psychiatric Association. Task Force on DSM‐IV. Diagnostic and Statistical Manual of Mental Disorders: DSM‐IV‐TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.
  21. Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. New York, NY: Springer; 2001.
  22. Marshall SW. Power for tests of interaction: effect of raising the Type I error rate. Epidemiol Perspect Innov. 2007;4:4.
  23. Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46:399424.
  24. Meagher DJ, Maclullich AM, Laurila JV. Defining delirium for the International Classification of Diseases, 11th Revision. J Psychosom Res. 2008;65:207214.
  25. McCusker J, Cole M, Abrahamowicz M, Primeau F, Belzile E. Delirium predicts 12‐month mortality. Arch Intern Med. 2002;162:457463.
  26. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291:17531762.
  27. Teres D, Brown RB, Lemeshow S. Predicting mortality of intensive care unit patients. The importance of coma. Crit Care Med. 1982;10:8695.
  28. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;1:480484.
  29. Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic‐ischemic coma. JAMA. 1985;253:14201426.
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Issue
Journal of Hospital Medicine - 9(12)
Issue
Journal of Hospital Medicine - 9(12)
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772-778
Page Number
772-778
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Impaired arousal at initial presentation predicts 6‐month mortality: An analysis of 1084 acutely ill older patients
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Impaired arousal at initial presentation predicts 6‐month mortality: An analysis of 1084 acutely ill older patients
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© 2014 Society of Hospital Medicine

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Address for correspondence and reprint requests: Jin H. Han, MD, Department of Emergency Medicine, Vanderbilt University Medical Center, 703 Oxford House, Nashville, TN 37232‐4700; Telephone: 615‐936‐0087; Fax: 615‐936‐1316; E‐mail: jin.h.han@vanderbilt.edu
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