1. PI Name And Affiliations

Oanh Kieu Nguyen, MD, MAS
Assistant Professor of Internal Medicine
UT Southwestern Medical Center, Dallas, Texas

2. Potential Co-Investigators

Anil N. Makam, MD, MAS, Assistant Professor of Internal Medicine, UT Southwestern (Co-PI)
Ethan A. Halm, MD, MPH, Professor of Internal Medicine, UT Southwestern
Potential Co-Investigators from collaborating HOMERuN and/or PCORnet CRG partner institutions TBD

3. Program Overview/Introduction

Vital sign instability on discharge could be a simple and clinically objective means of assessing patient readiness and safety for discharge. Our research group has previously shown that the number of vital sign instabilities on discharge is associated with higher rates of 30-day readmission and death in 6 diverse north Texas hospitals. However, several key gaps remain, including 1) unknown national prevalence of vital sign instability among hospitalized patients; 2) reasons why patients are discharged despite the presence of vital sign instability on discharge; and 3) the effectiveness of interventions to reduce vital sign instability on discharge and/or post-discharge adverse outcomes. We propose to: assess the epidemiology of vital sign instability among hospitalized adults at discharge in a more generalizable cohort of hospitals and regions; assess why patients with vital sign instabilities are discharged; and develop and pilot a multifaceted intervention to optimize post-discharge adverse outcomes among patients identified as having vital sign instability on discharge. Our findings will be foundational to developing evidence-based discharge criteria and interventions to optimize patient outcomes, safety, and recovery during the transition from hospital to home and after hospital discharge for patients known to be at higher risk for adverse outcomes.

Our proposed study is aligned with the overall HOMERuN mission to ensure that hospitalized patients receive ‘the best quality, safest, and highest value care from hospitalization through recovery’ and with the specific HOMERuN research priorities of 1) focusing on general medicine patients cared for by hospitalists; 2) increasing collaboration across hospital medicine groups and researchers; 3) optimizing the effectiveness and safety of care transitions; and 4) improving post-discharge patient safety.

4. Key Clinical Questions (PCORI Decisional Dilemma And Gap Analysis)

a) What is the epidemiology of vital sign instability among hospitalized adults at discharge?
b) Why are patients with vital sign instabilities discharged instead of remaining in the hospital?
c) Does a multifaceted intervention improve vital sign stability at discharge and/or post-discharge adverse outcomes?

5. Aims And Hypotheses

Our overall aim is to assess the epidemiology of and reasons why hospitalized adults with vital sign instability are discharged in order to develop and evaluate an intervention to improve management of patients with vital sign instability and reduce subsequent adverse post-discharge outcomes.

SPECIFIC AIM 1: Describe the prevalence of vital sign instability on discharge among hospitalized adults, key clinical characteristics of this population, disposition status, and association of vital sign instability with adverse post-discharge outcomes, including hospital readmission and mortality at 30, 90, and 180 days.

Hypothesis 1: We hypothesize that 1 in 5 adults will have at least 1 vital sign instability on discharge, and that the number (and combination) of vital sign instabilities will be strongly associated with worse post-discharge outcomes even after adjusting for other prognostic factors and post-discharge location.

SPECIFIC AIM 2: Assess reasons for discharging patients with vital sign instability, using a mixed methods approach with both structured chart reviews and interviews of hospitalists.

Hypothesis 2: We hypothesize that there will be three main themes for discharging patients with vital sign instability: 1) known advanced acute or chronic illness not amenable to further in-hospital treatment; 2) known vital sign instability with plan for stabilization at post-acute care facility; and 3) vital sign instability present but not recognized by clinical care team. Furthermore, we anticipate suboptimal rates of goals of care discussion and end-of-life planning prior to hospital discharge.

SPECIFIC AIM 3: Develop and pilot a multifaceted and tailored intervention to reduce vital sign instability and adverse post-discharge outcomes among hospitalized adults.

Hypothesis 3: The intervention will be informed by Aims 1 and 2. We hypothesize that a multi-component intervention may consist of at least: 1) automated best practice alert if vital sign instabilities are present; 2) recommendation to delay discharge until vital signs are stable for at least 24 hours; and/or 3) recommendation for goals of care discussion, palliative care, and/or hospice referral as appropriate if further in-hospital treatment is not warranted.

6. Preliminary Data

Our group conducted a previous AHRQ R24-funded study assessing the association between vital sign stability at hospital discharge and 30-day readmissions and mortality using electronic health record data from a diverse cohort of 6 hospitals in north Texas. (1) In our cohort of 32,835 adults hospitalized on all medicine services, 19% were discharged with at least one vital sign instability and 3% had two or more vital sign instabilities. Overall, 13% of individuals with no instabilities died or were readmitted compared to 17% with 1, 21% with 2, and 26% with 3 or more instabilities. The presence of any vital sign instability was independently associated with higher risk-adjusted odds of the composite outcome of death or readmission within 30 days (AOR 1.36, 95% CI 1.26-1.48), and was more strongly associated with death (AOR 2.31, 95% CI 1.91-2.79) than readmission. Although a smaller proportion of the population had two or more instabilities, the adjusted odds of death more than tripled among this high-risk group compared to those with no instabilities (AOR 3.3, 95% 2.5-4.9).

We also found that the greater the number of vital sign instabilities an individual had on discharge, the more likely they were to be discharged to a post-acute care facility (i.e., nursing homes, skilled nursing facilities, and long-term acute care hospitals). Only 18% of individuals with no instabilities were discharged to post-acute care, compared to 22% of those with one instability, 26.7% of those with two instabilities, and 43% of those with three or more instabilities (p<0.001 for trend). Additionally, individuals with vital sign instabilities discharged to post-acute care facilities had far higher rates of post-discharge adverse events compared those who were sent home. Among individuals with two instabilities, 12% of individuals discharged to a post-acute care facility died within 30 days compared to only 2% of those discharged home (p<0.001 for comparison).

Our study was the first to assess the association between vital sign instabilities and discharge and 30-day mortality and readmission among all adults on medical inpatient services. Although our findings confirm and extend the landmark studies by RAND (2) and Halm et al (3), which assessed the effect of more broadly defined clinical instabilities on discharge in groups with selected conditions in the 1980s and 1990s respectively, several key limitations and knowledge gaps remain. First, the generalizability of our findings beyond the Dallas-Fort Worth metroplex is unknown, especially given the very high post-acute care utilization in this region. Although we included a large sample of diverse patients treated in a variety of settings (one safety net teaching hospital and 5 community non-teaching hospitals), extending our study to HOMERuN CRG institutions (which include a mix of academic/university and community teaching and non-teaching settings) would significantly enhance the external validity or our findings. Second, we were unable to ascertain the reasons and modifiability of vital sign instability on discharge – i.e., patients discharged with unstable vital signs may have had advanced or terminal illness that was otherwise not treatable. Furthermore, among patients known to have advanced or terminal illness, we do not know whether these patients had a goals of care discussion prior to hospital discharge. We were unable to ascertain this information given the limitations of our dataset. Finally, it is unknown whether an intervention strategy targeting individuals with vital sign instabilities would result in stabilization and/or fewer post-discharge adverse events among hospitalized adults. This information is critical to informing the development of objective, evidence-based hospital discharge criteria to optimize post-discharge patient safety.

Use of the HOMERuN CRG data and resources will allow us to validate and extend our prior findings, and develop and pilot an intervention in a more nationally representative cohort of hospitalized adults. Findings from this proposal will form the basis for follow-on multi-site pragmatic cluster randomized controlled trial of our newly developed intervention strategy to reduce vital sign instability on discharge and adverse post-discharge outcomes.

7. Study Design, Including Study Subjects (Patients And/Or Providers) And Setting, Comparator Groups, Data Sources, Outcomes, Analysis Plan, Power And Sample Size, Limitations, And Timeline

SPECIFIC AIM 1:
Study Design, Subjects and Setting: Observational descriptive cohort study of hospitalized adults ≥18 years old cared for on a medicine service

Data Sources: PCORnet Clinical Data Research Network augmented with electronic health record data (EHR) from participating sites, and EHR from 31 hospitals in the Southwestern Health Resources (SWHR) an integrated regional health care network and accountable care organization (ACO) in north Texas that spans a 16-county service area with more than 6 million residents. All SWHR hospitals use the Epic EHR system.

Outcomes: Demographics of patients; frequency and timing of vital sign instabilities on the day of discharge; disposition status (home versus post-acute care), readmissions to the index hospital at 30, 60, and 90 days; mortality at 30, 90, and 180 days

Analytic Plan: Descriptive analyses for prevalence/frequency of vital sign instabilities. To assess the association between vital sign instability and adverse post-discharge outcomes, we will use logistic regression adjusting for sociodemographic characteristics, prior utilization history, principal diagnosis, measures of severity of illness (i.e., selected laboratory abnormalities) comorbidities, hospital complications. We will account for clustering by hospital using generalized estimating equations.

Power and Sample Size: To be determined, depending on number of participating sites.

Anticipated Challenges: We anticipate challenges related to limited availability of data needed to complete this Aim, including: 1) Inconsistent availability of inpatient data on vital signs; 2) incomplete ascertainment of 30-day readmissions, as information will be limited to readmissions to the index hospitalization; and 3) incomplete ascertainment of mortality up to 180 days after hospitalization and in PCORNet. These limitations would be overcome with expanded PCORnet data collection.

One limitation to conducting this study within HOMERuN and/or PCORnet sites is uncertain generalizability to other hospital populations given the overrepresentation of tertiary referral hospitals. The inclusion of community SWHR hospitals in our study cohort will help mitigate this limitation.

Proposed Expansion of PCORnet Data Collection: Expand vital sign collection to extend to all recorded vital sign measurements from inpatient settings on the first and last days of hospitalization; expand ascertainment of mortality to include deaths occurring up to 180 after hospitalization; expand ascertainment of readmissions to include readmissions at any area hospitals (i.e., within catchment area of index hospital)

Timeline: 1-2 years, depending on data availability (years 1-2 of R01)

SPECIFIC AIM 2:
Study Design, Subjects and Setting: Mixed methods study with structured chart review and qualitative interviews of hospitalists

Data Sources: EHR and hospitalist physicians from participating sites

Analytic Plan: We will perform a structured chart review and conduct recall interviews with the treating hospitalists of patients identified with unstable vital signs to elicit reasons for discharge. Among patients identified as having known severe illness, we will assess whether patients had a goals of care discussion, DNR order, and/or palliative care consult. We will conduct descriptive analyses of structured chart review and thematic analysis of interviews and discharge summaries.

Power and Sample Size: 1,000 patients across PCORnet/HOMERuN CRG sites, and SWHR hospitals, or until reaching thematic saturation

Anticipated Challenges: Logistical challenges including 1) reciprocity of IRBs; 2) obtaining data for chart review across sites; 3) conducting interviews across sites; and 4) maintaining fidelity of data abstraction and collection across sites. To overcome these challenges, we would leverage the established expertise of HOMERuN mentors and collaborators in performing multi-site mixed methods studies consisting of chart review and qualitative interviews, given the parallels in our proposed research strategy to methods employed in a previous HOMERuN study assessing the preventability of hospital readmissions. (4)

Additionally, limiting this study to only HOMERuN and/or PCORnet sites may result in uncertain generalizability to other hospital populations given the overrepresentation of tertiary referral hospitals. The inclusion of community SWHR hospitals in our study cohort will help mitigate this limitation.

Timeline: 2 years (years 2-3 of R01)

SPECIFIC AIM 3:
Study Design, Subjects and Setting: Informed by Aims 1 and 2, we will conduct a pilot study of a multifaceted intervention at UT Southwestern Medical Center and one THR community hospital in the DFW metroplex. We hypothesize that this intervention will include 1) automated best practice alerts to notify physicians of the 2 or more presence of vital signs at the time of discharge; 2) automated clinical decision support to recommend tailored interventions including but not limited to a) extending hospitalization; b) structured communication with post-acute care facilities; and/or c) referral for palliative and/or hospice care.

Outcomes and Analytic Plan: We will assess feasibility and acceptability of our intervention using validated constructs as per the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance). These are primarily descriptive analyses to assess the reach, feasibility, and adoption of the intervention. We will conduct a preliminary analysis of the effect of readmissions and deaths at 30, 90, and 180 days with an interrupted time series (ITS) and difference-in-difference (DiD) designs. The ITS design will use the two participating hospitals’ historical data as a control. The DiD analysis will include two other THR hospitals in the DFW metroplex as a reference.

Power and Sample Size: N/A; feasibility study which will inform sample size for multi-site pragmatic RCT

Anticipated Challenges: We anticipate two key challenges: 1) EHR interoperability between UT Southwestern and THR hospitals. All hospitals in the SWHR ACO use the Epic EHR system. By years 3-5 of this R01, we anticipate that SWHR will have a unified data warehouse/repository to allow extraction of EHR data to facilitate our data collection strategy. 2) Ascertainment of hospital readmissions. We will mitigate this challenge by using data on readmissions from a regional all-payer administrative claims database through the Dallas-Fort Worth Hospital Council, which includes data on hospitalizations from 136 hospitals within a 100-mile radius of Dallas, accounting for over 95% of the catchment area.

Timeline: 2 years (years 4-5 of R01)

8. Characteristics Of Sites Who Might Participate

We preferentially seek participation from hospital sites with the following characteristics:

1. Sites with a local champion for hospital medicine research;
2. Sites with experience extracting and using electronic health record (EHR) data for hospital medicine research;
3. Member of either the HOMERuN and/or PCORNet CRGs;
4. (Optional) Sites who have access to regional all-payer claims data to enable ascertainment of utilization and outcomes outside of the site of index hospitalization;
5. Sites that maximize diversity and representativeness of included populations to the general population of hospitalized adults in the U.S.

9. Potential Funders With RFA/RFP And Due Dates (If Known)

We plan to seek R01 funding for this work through the following potential funders:

• AHRQ R01: PA-14-291, AHRQ Health Services Research Projects. This project is aligned with the AHRQ priority areas of patient safety and use of health information technology to improve patient outcomes
• NIA R01: PA-16-160, Investigator-Initiated NIH Research Project Grant. This project is aligned with the NIA priority areas to support research on health services for older adults with multiple chronic conditions, and with the strategic priority to support demonstration/pilot projects for pragmatic clinical trials
• NHLBI R01: PA-16-160, Investigator-Initiated NIH Research Project Grant. This project is aligned with the NHLBI research priority to optimize clinical and implementation research to improve health and reduce disease through leveraging EHRs

Potential non-R01 funders include the following:

• PCORI: Cycle 3, Improving Healthcare Systems
• https://www.pcori.org/funding-opportunities/announcement/improving-healt...) – LOI deadline Oct 31, 2017
• AHRQ R18: PA-17-261, Developing New Clinical Decision Support to Disseminate and Implement Evidence-Based Research Findings
• Moore Foundation: This work is aligned with the Foundation’s priority areas of improving patient safety and improving the experience and outcomes of patients with serious illness
• The Commonwealth Fund: This work is aligned with the Commonwealth Fund’s priority area of health care delivery system reform for individuals with multiple serious chronic conditions

REFERENCES

1. Nguyen OK, Makam AN, Clark C, et al. Vital Signs Are Still Vital: Instability on Discharge and the Risk of Post-Discharge Adverse Outcomes. Journal of general internal medicine. Jan 2017;32(1):42-48.
2. Kosecoff J, Kahn KL, Rogers WH, et al. Prospective payment system and impairment at discharge. The 'quicker-and-sicker' story revisited. JAMA : the journal of the American Medical Association. Oct 17 1990;264(15):1980-1983.
3. Halm EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA : the journal of the American Medical Association. May 13 1998;279(18):1452-1457.
4. Auerbach AD, Kripalani S, Vasilevskis EE, et al. Preventability and Causes of Readmissions in a National Cohort of General Medicine Patients. JAMA Intern Med. Apr 2016;176(4):484-493.