The introduction of highly active antiretroviral therapy (HAART) about 15 years ago has dramatically improved overall survival among persons infected with HIV.1–3 However, although admissions related to advanced AIDS and opportunistic infections have declined significantly in the post-HAART era, the rate of inpatient admission for any cause among HIV-infected individuals remains relatively high4–6 with a slow rate of decline.7 Women,5,7–10 African Americans,5,7,11 injection drug users,5,7,8,12–14 those with mental illness,13,15 those not receiving HAART,4,9 and those with low CD4 counts12,14 are significantly more likely to be admitted to the hospital. Readmission among HIV-infected individuals is common8,10,16 and is influenced by both medical and social factors.16–18
The high rate and cost of hospital readmission among the elderly has been the source of considerable research and policy interest.19 The greatest attention to date has been on efforts to reduce the risk of readmission among patients with congestive heart failure, pneumonia, and myocardial infarction—the 3 most common medical reasons for hospitalization among Medicare beneficiaries. Other costly conditions, such as HIV, have been less well studied and merit serious attention. Data from 6 states in 2004 found that a single HIV admission costs more than $15,000, with an average length of stay of 8.4 days, considerably longer than most hospitalizations in the non-HIV population.20,21 Efforts to better understand, predict, and reduce readmissions among patients infected with HIV have the potential to improve patient outcomes and decrease costs.
To prevent readmissions, a rapid and reliable method to assess and predict readmission risk is needed early in the index admission. Unfortunately, physicians, case managers, and nurses are not able to accurately predict readmissions using standard approaches.22 The best performing models of the risk of 30-day readmission have been disease specific and incorporate detailed data on both clinical and social factors.23–25 The increasing use of comprehensive electronic medical records (EMRs) provides the opportunity to develop sophisticated risk prediction rules harnessing the broad range of detailed information available electronically.
This study sought to (1) characterize the rates and reasons for readmission with 30 days of discharge among patients hospitalized with HIV, (2) develop and validate a model to predict 30-day risk of readmission, based on a diverse set of clinical and social factors ascertainable from the EMR in the first 48 hours of admission, and (3) characterize rates of 30-day rates of death and factors associated with mortality.
Study Population, Data Source, and Variables
The study focused on HIV-infected patients hospitalized on the internal medicine service between March 1, 2006 and November 30, 2008 at Parkland Memorial Hospital, a large urban teaching hospital in Dallas, TX. Parkland Health and Hospital System (Parkland) is an integrated delivery system, which also includes a network of 11 adult-oriented community outpatient clinics, including a focused HIV clinic. It is the sole public safety net provider in Dallas County. This study focuses on patients with a principal or secondary discharge diagnosis of HIV or AIDS (based on ICD-9 codes 042 and V08). All variables were extracted from the Epic EMR (EPIC Systems Corporation, Verona, WI) of the health system.
Outcome Variables—Readmission and Mortality
We developed 2 separate models among patients hospitalized with HIV, one for risk of readmission for any cause within 30 days of discharge and a different one predicting risk of death within 30 days of discharge. Readmission was defined as an inpatient admission for any cause to any hospital within a 30-day period from the index discharge. If a readmission occurred after 30 days of an HIV index admission discharge, it was considered as another index admission. For the mortality model, all index admissions were included. For the readmission model, we excluded all index admissions that resulted in death within 30 days of discharge.
We identified readmissions to any hospital in the area using a data linkage service available through the Dallas-Fort Worth Hospital Council that maintains a regional hospital discharge data set of all admissions to 70 acute care hospitals in North Texas.26 Survival in the 30 days after discharge was ascertained by querying the Parkland inpatient and outpatient clinic data systems for evidence of a follow-up encounter more than one month after the index hospitalization. For patients lacking an EMR encounter in the 30 days after discharge, we searched the Social Security Death Index.
We extracted a large number of candidate risk factors according to 3 criteria. The variable needed to be (1) available in the EMR, (2) routinely collected or available within the first 48 hours of hospital presentation, and (3) determined by consensus of an interdisciplinary team as reasonably available to most hospitals with a basic EMR.
We developed a conceptual framework of readmission based on the existing literature and clinical expertise on comorbidities and treatments.27 We identified 2 major categories of risk predictors, clinical and nonclinical variables. Clinical factors included HIV/AIDS severity, laboratory test results, mental health history, and HIV medication regimens. Nonclinical variables included sociodemographics, social instability (eg, number of home address changes in the prior year, homelessness, and lack of emergency contact information); health-risk behavior (eg, history of confirmed cocaine, opiate use during the past year using specific ICD-9 CM codes); adherence measures (eg, history of missed clinical appointments and leaving against medical advice); and prior acute health care utilization [hospitalizations and emergency department (ED) visits]. We also included a composite neighborhood measure of social “disadvantagedness” based on median household income, percent of households below the poverty level in the census tract, percent of residents with age >18 years, who reported with less than college or higher education, and percent of population who were non-white. The data were reported by the US Census Bureau for the 2000 census for 1046 census tracts in the 12-county area surrounding Dallas County. Census tract scores were used to rank the tracts into quintiles with the lowest one classified as a high-risk census tract.
Before model development, we examined all available variables for missing values. For analyses with continuous variables (age, length of stay, laboratory score, etc), we allowed case-wise deletion because we found missing values to be rare. For each categorical variable, we created a response level for grouping cases with missing values, allowing us to keep these cases in the analysis.
Derivation of the Electronic Readmission Models
The process of model building involved 4 stages. First, we examined the univariate relationship between the outcome variable readmission and each of the clinical and nonclinical categorical variables through logistic regression at threshold significance of P ≤ 0.20. We examined continuous variables (eg, age, number of prior ED visits, and inpatient admissions) for nonlinear effects by testing the contributions of spline functions and variable transformations.
We split each continuous laboratory variable into distinct categories using recursive partitioning to determine limit values (using RTREE).28 Second, to protect against excess overfitting, we restricted the number of predictor variables to that estimated through a heuristic shrinkage formula.29 Third, candidate variables were ranked by P value using bootstrapping in 1000 multivariate logistic regression iterations.30 In the fourth stage, we included variables that were selected based on conceptual and statistical significance to fit the final model. To account for the effects of patients with more than one index admission, we used robust variance–covariance matrix estimators for computing standard errors for model coefficients.31 The process was repeated for modeling mortality, resulting in a different set of covariates and coefficients.
The models were validated using several approaches. Model discrimination was assessed by the c statistic. Model calibration was evaluated using the Hosmer–Lemeshow χ2 goodness of fit test. We internally validated the model using a cross-validation methodology29,32 and stratified our cohort by risk quintiles. In this approach, the full sample was split randomly without replacement into derivation (50%) and validation (50%) subsamples 1000 times. The model was reconstructed for each of the derivation samples using stepwise regression and then tested on the corresponding validation subsample. The c statistics for the derivation and validation subsamples were then computed in each iteration and averaged across all iterations. Using interval endpoints determined by the derivation subsamples, 5 readmission risk categories (1 = very low to 5 = very high) were created based on quintiles of predicted risk and were graphically assessed by comparing derivation and validation subsample results. To assess the association between readmission time and the predicted risk, Kaplan–Meier curves were constructed for the stratified risk groups.
All analyses were conducted using STATA statistical software (version 10.0; STATA Corp, College Station, TX) and RTREE (from http://peace.med.yale.edu/pub). The University of Texas Southwestern Medical Center Institutional Review Board approved the research protocol.
Description of the Study Cohort
During the 32-month study period, there were 2476 index admissions among 1509 unique HIV-infected individuals. Two-thirds (1000, 66%) of individuals had only one index admissions, 291 (19%) had 2 index admissions, and the remaining individuals (218, 14%) had 3 index admissions. The characteristics of the study cohort are shown in Table 1. Three-quarters of admissions were among patients who were males (73%), more than half were African American (57%), and the mean age was 43 (SD = 9.4) years. More than half of admissions had a CD4 <200, and a quarter had an AIDS-defining illness within the year before admission. The average length of stay was 7 days.
Predictors of 30-Day Risk of Readmission
Overall, one in 4 admissions resulted in a readmission within 30 days of discharge (25.2%, N = 623). More than 3-quarters of readmissions within 30 days were to the index hospital (77.8%). When the cohort is limited to those index admissions that did not result in death within 30 days of discharge (N = 2402), the readmission rate was similar (24.4%, N = 586).
The largest proportion of all-cause readmission were among those with a principal diagnosis at the index admission of HIV/AIDS (41%), followed by other infections (10%), cancer (6%), gastrointestinal bleeding (4%), congestive heart failure (3%), and renal failure (3%) (Table 2). The highest rates of readmissions were among those with an index admission for cancer, congestive heart failure, renal failure, and gastrointestinal disorders (Table 2).
In the univariate analyses, a large number of domains and variables were associated with risk of readmission (Table 3), including living situation, HIV/AIDS severity, mental health, substance use, laboratory abnormalities, insurance status, and prior ED visits/hospitalizations. Results of multivariate analysis for readmission are shown in Table 4. A broad range of clinical factors were associated with risk of readmission, including AIDS defining illness, CD4 ≤ 92, and renal, hepatic, and hematologic abnormalities. In addition, patients who were homeless, insured by Medicaid, and had higher rates of utilization of inpatient and emergency department services were more likely to be readmitted within 30 days of release. Linear shrinkage analysis did not reveal overfitting.
Predictors of 30-Day Risk of Death
The rate of death within 30 days of discharge was 3.0% (N = 74). A social security number was not available for 9% of patients and, therefore, 30-day mortality through the social security death index was unavailable for these subjects. Laboratory abnormalities, including renal failure, acidosis, liver abnormalities, anemia, and immunosuppression, rather than social factors, were the most important predictors of mortality in both univariate and multivariate analyses for mortality (Tables 3 and 5).
The electronic readmission model produced an overall c statistic of 0.72 [95% confidence interval (CI): 0.70 to 0.75]. The average c statistics from the cross-validation analysis were 0.72 (95% CI: 0.69 to 0.74) and 0.70 (95% CI: 0.67 to 0.72) for the derivation and validation samples, respectively.
The electronic model was capable of stratifying patients across a wide range of risk for readmission from 8% to 45%, and derivation and validation subsamples were highly concordant across the risk spectrum (Fig. 1). Patients in higher risk categories of the electronic model were readmitted earlier over the 30-day postdischarge period in a Kaplan–Meier analysis (P < 0.001, Fig. 2). For the electronic mortality model, the overall c statistic was 0.79 (95% CI: 0.74 to 0.84).
In this study of 2476 admissions among HIV-infected patients treated in a large urban safety net hospital, we found that 1 in 4 admissions resulted in a readmission within 30 days of discharge. Although there are limited published data on HIV readmission rates, 2 prior studies reported 14-day readmission rates among HIV patients with pneumonia of13%–19%.16,17 Our 30-day readmission rate is similarly high and is comparable to readmissions for congestive heart failure (21%–26%),24,33,34 and higher than published readmission rates for acute myocardial infarction (18.9%)35 and pneumonia (17.4%).36
We also developed an innovative EMR-derived multivariate model that accurately predicted 30-day readmission risk among HIV inpatients. This study extends an advancing field of work that successfully characterizes patient risk based on data available in the EMR.24,37–39 A broad range of clinical and nonclinical variables contributed to this prediction model, including HIV-related factors, such as CD4 count and a history of AIDS-defining illness; laboratory abnormalities, such as renal, hepatic, and hematologic abnormalities; and living situation, health insurance, and health care utilization.
Several studies have sought to characterize individual clinical and social factors that may increase the risk of readmission among HIV-infected patients. Palepu et al,16 in a retrospective case-control study, found that among HIV patients admitted with pneumonia, those who left against medical advice, those who lived in the poorest urban neighborhoods, and those who had been hospitalized in the past 6 months were at highest risk for readmission. Similarly, Grant et al,17 in a separate study of HIV patients admitted with pneumonia, found that patients who did not have a companion at discharge or who reported crack cocaine use were at higher risk for readmission. Noysk et al,18 in a propensity score matched analysis, found that taking HAART significantly reduced a patient's risk for readmission.
Our findings confirm and extend the data from these prior studies. We found that homelessness, living far from the hospital, Medicaid insurance, and frequent inpatient and emergency room health care utilization were important components in our prediction model. These results suggest that nonclinical factors may be contributing to readmissions, including housing instability, transportation, socioeconomic status and possibly poor engagement in outpatient care. Surprisingly, mental health issues and substance use, which were seen in 41% and 31% of inpatients respectively, and were correlated with readmission in univariate analyses, did not improve the performance of our multivariate prediction model. This was probably because other measures of social disadvantage were more important.
This study also provides data on the epidemiology of hospitalizations among patients with HIV. Not surprisingly, these patients were predominately male minorities with many social disadvantages and were severely immunocompromised. HIV/AIDS was the most common primary diagnosis at the time of index admission, and these patients accounted for a large proportion of readmissions (41%). Other infections were the next most common reason for readmission (10%). More than half of the patients had a CD4 count <200 cells/mm3 and 60% of these had a CD4 count <50 cells/mm3. Although other studies have shown that reasons for hospitalization among HIV patients has shifted from AIDS-defining illnesses to chronic end-organ diseases,6,12 our study emphasizes that AIDS is still a common cause of hospitalization. In addition, African Americans and Hispanics together comprise 74% of our cohort and nearly half of all patients were living in a census tract in the lowest socioeconomic quintile in Dallas. The overrepresentation of minorities and underserved individuals in the inpatient population highlights the severity of the HIV epidemic in Texas,40 especially among African Americans. Low CD4 cell counts and hospitalizations in this group may be partially explained by low rates of HAART utilization.11,41,42
Despite clinical indications for treatment, more than half of the patients in this study had no history of antiretrovirals (ARVs) being prescribed within the Parkland system, and approximately 25% of patients in this study did not fill their ARV prescription in the 30 days before admission. More than 20% had missed scheduled outpatient appointments in one of 11 clinics in the health system. To avoid complications due to HIV and related hospital admissions, patients need to adhere to both their ARVs and their outpatient clinic visits.43–45 Engagement in care, including both linkage to care and retention in care, has become an important focus among HIV providers and researchers, with implications for individual outcomes, including improved mortality,43,46,47 and population-level outcomes, such as reducing racial and socioeconomic disparities in health care and transmission of disease.43,48,49 To improve the high rates of 30-day readmission among HIV patients in our hospital system, recent efforts include providing clinic appointments within 2 weeks of discharge from the hospital and an ongoing in-depth chart review to identify preventable causes of readmission. Dallas County Health and Human Services also has a new outreach initiative to locate HIV-infected individuals who have been lost to care.
Several limitations are worth noting. Our study was based at a single urban safety net hospital serving predominantly poor minorities, so generalizability to other settings and patient populations is unknown. However, ours is the largest study on readmissions among HIV patients to date, and this population is one that carries the biggest burden of HIV. We had the advantage of being able to extract data from both inpatient and outpatient health information systems to create a richer and more longitudinal profile of patients and their risk factors. These results may not apply to hospitals lacking EMRs or those without any outpatient care data. Nonetheless, in considering potential predictors, we favored the selection of elements that would be reasonably available to hospitals with a basic EMR. The adoption of EMRs is accelerating; thus, automated models are likely to have wider application value in the near future. Another limitation is missing data, such as CD4 and viral load values, before admission. However, because our hospital system cares for most HIV patients in the county, we believe that this reflects a real-world setting where a large proportion of HIV-infected patients are not engaged in routine HIV care.50 Finally, although we used rigorous statistical methods to validate our model, our validation was limited to our internal data set. Future efforts should validate the model prospectively and optimally in other institutions and settings.
These findings have implications for both clinical care and health policy. Clinicians should recognize that HIV patients are at high risk for readmission and will need to more effectively engage patients, families, case management, and other services early during a hospitalization to address risk factors for readmission. From a policy perspective, this work highlights the powerful impact of both clinical and nonclinical factors on risk of readmission in HIV. Many of the social disadvantage and behavioral risk factors may be things that providers have little direct influence over and have nothing to do with the quality of inpatient or postdischarge care. However, these types of EMR-enabled disease-specific prediction models could prove useful in identifying those at highest risk who should be the focus of case management resources which are often quite limited in most safety net health systems. In addition, information on the specific things that put an individual at risk for readmission or death (clinical vs. social) could help facilitate a more patient-tailored approach to improving the transition of care.
Future research should explore the causes of readmission among HIV-infected patients in greater detail and determine what proportion of readmissions may be potentially preventable. These findings could inform future interventions, building upon prior successful linkage to care programs, such as the ARTAS case management intervention,51 based on promoting self-efficacy and project CONNECT,52 which involves client-oriented navigation. In addition, external and prospective validation of the EMR prediction model is needed, including using this model in real time. Once validated, the EMR model can be used to stratify hospitalized patients based on their readmission risk, thereby helping direct resources and interventions to those who may derive the greatest benefit.
The authors thank the Dallas-Fort Worth Hospital Council Foundation for assisting in the collection of posthospitalization data through the information sharing initiative.
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