Association of Inpatient Opioid Utilization and Readmission Risk in Sickle Cell Disease

Abstract Background: Vaso-occlusive crisis (VOC) is the hallmark complication of sickle cell disease (SCD). The majority of SCD-related healthcare costs in the United States, estimated at $2.4 billion annually, are attributed to frequent healthcare utilization due to recurrent VOC (1-3). Risk factors such as the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) only without opioids, older age, and steroid treatment have been identified to be associated with readmissions in pediatric SCD patients (4, 5), but limited data exist about potential predictors for readmission in adults (6). The impact of inpatient opioid utilization on readmission was evaluated in this study. Methods: Seventy SCD adults treated at the University of Illinois Hospital from 2012-2016 had at least one hospitalization for uncomplicated VOC that was followed by a 30-day readmission (30-DR) and at least one hospitalization without a 30-DR. One hospitalization with a 30-DR and one hospitalization without a 30-DR from each patient were used to form the discovery cohort (a total of 140 hospitalizations from 70 unique patients). Patient characteristics, inpatient laboratory values, outpatient daily opioid use before admission, and inpatient daily opioid use were collected from the electronic medical records, and the ratio of the last inpatient day opioid dose/home opioid dose before admission was calculated. Among the 70 patients in the discovery cohort, 22 patients had more than one hospitalization with a 30-DR. The additional hospitalizations with a 30-DR and matched hospitalizations from the same patient without a 30-DR were used to form a validation cohort (a total of 62 hospitalizations from 22 unique patients). A Wilcoxon signed-rank test was performed to compare the ones with a 30-DR to the ones without. The study was approved by the Institutional Review Board prior to the initiation of chart review. Results: Among the 70 SCD patients identified, the median (IQR) age was 32.5 (25-44) years by the time of the first admission included in this cohort, and 67% were females, 76% were HbSS or Sbeta0 genotype, and 46% were on hydroxyurea before admission. The median (IQR) dose of daily outpatient opioids before the first admission was 170 (64-280) mg oral morphine equivalents (OME). When the hospitalizations without a 30-DR were compared to the ones with in the discovery cohort (Table 1), the ratio of last inpatient day opioid dose/home opioid dose was lower (1.5 vs. 1.9, p=0.024), whereas other relevant clinical variables including length of stay, pain score upon discharge, and hemoglobin or WBC upon discharge were not significantly different between the two groups (Table 1). The proportion of patients who used patient controlled analgesia (PCA) during admission, or underwent opioid dose tapering during hospitalizations, or converted IV opioids to oral ones before discharge was also comparable. In the validation cohort (Table 1), the ratio of last inpatient day opioid dose/home opioid dose in the group without a 30-DR was also lower than the ones with a 30-DR (1.4 vs. 2.0, p=0.033), whereas other clinical variables were comparable. Summary: Here we showed that a high ratio of last inpatient day opioid dose/home opioid dose is associated with readmission risk for sickle cell patients treated for uncomplicated VOC. The results suggest that proper tapering of inpatient opioid dose in reference to patient's home opioid dose before discharge may reduce the readmission risk. Reference: K. L. Hassell, Am J Prev Med38, S512 (Apr, 2010). S. Lanzkron, C. P. Carroll, C. Haywood, Jr., Am J Hematol85, 797 (Oct, 2010). T. L. Kauf, T. D. Coates, L. Huazhi, N. Mody-Patel, A. G. Hartzema, Am J Hematol84, 323 (Jun, 2009). L. M. Okorji, D. S. Muntz, R. I. Liem, Pediatr Blood Cancer64, (May, 2017). A. Sobota, D. A. Graham, E. J. Neufeld, M. M. Heeney, Pediatr Blood Cancer58, 61 (Jan, 2012). M. A. Brodsky et al., Am J Med130, 601 e9 (May, 2017). Disclosures No relevant conflicts of interest to declare.

Download Full-text

The Vitamin D Receptor Gene and Disease Severity in Sickle Cell Anemia

Blood ◽

10.1182/blood.v118.21.2122.2122 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2122-2122

Author(s):

E. Leila Jerome Clay ◽

Alison Motsinger-Reif ◽

Janelle Hoskins ◽

Lindsay Veit ◽

David A. Barrow ◽

...

Keyword(s):

Blood Pressure ◽

Vitamin D ◽

Sickle Cell Disease ◽

Disease Severity ◽

Sickle Cell ◽

Severity Score ◽

Validation Cohort ◽

Cell Disease ◽

Discovery Cohort ◽

Severity Scores

Abstract Abstract 2122 Vitamin D is important in multiple aspects of health, including the cardiovascular, immune and skeletal systems and its effects are mediated through the vitamin D receptor (VDR). The systems affected by vitamin D are also perturbed by sickle cell disease (SCD). Vitamin D deficiency is common in SCD, but its contribution to disease manifestations is not yet known. In normal populations, vitamin D has been shown to be associated with hypertension and vascular pathology. That association may be particularly relevant to the inflammatory / endothelial damage seen in sickle cell disease. We have used clinical and laboratory data to create separate inflammatory and vaso-occlusive severity scores. Our hypothesis is that specific VDR polymorphisms are associated with disease severity in sickle cell disease. DNA specimens from 1141 study participants in the NIH-funded Silent Infarct Transfusion (SIT) trial were used. In this multi-center international trial, the participants were children ages 4 to 13 years of age with SCD who were screened for the presence of silent cerebral infarction and had demographic and clinical data collected, as well as samples for a biologic repository for a self-renewing source of DNA. An initial 570 samples served as the discovery cohort. The subsequently enrolled 530 individuals formed our validation cohort. We evaluated 79 single nucleotide polymorphisms (SNP) in the VDR gene and three associated genes, CYP27B1, VD binding protein, retinoid X receptor, and tagging SNPs from the African American population from Hapmap. The discovery cohort individuals had VDR haplotype information from a prior genome-wide association study (GWAS), and analysis for additional VDR-related SNPs was performed using a specifically designed Sequenom assay. The validation cohort was analyzed for SNPs that were significant in the discovery cohort. Phenotype data was obtained from the demographic and clinical information of the participants, and was used to create the severity scores. The vaso-occlusive score includes: number of hospitalizations for pain, number of hospitalizations for acute chest, and avascular necrosis. The inflammatory severity score includes: priapism, transient ischemic attacks (TIA), silent cerebral infarct, systolic and diastolic blood pressure, transcranial doppler velocity, white count and baseline hemoglobin. The overall severity score includes all of the inflammatory and vaso-occlusive variables. To derive the scores, the variables were transformed into quartiles. Each individual subject was assigned values of 1, 2, 3, or 4 for each variable with 1 representing lowest severity and 4, the highest. In addition, in concert with prior analyses of the SIT data, the variable for number of hospitalizations for pain was used alone as a severity measure. The severity scores were not normally distributed and were not totally continuous distributions, so the Kruskal-Wallis test was used in association analysis. To look for complex genetic models including potential gene-gene interactions for prediction of disease severity, the Multifactor Dimensionality Reduction (MDR) method was utilized, with repeat analyses performed for each severity score. By univariate analysis, no associations were found between any of the VDR associated SNPs and the 3 severity scores. Using MDR in the discovery cohort, one SNP, rs7965281, was found to be associated with the inflammatory severity score. It remained significant after correcting for multiple comparisons with permutation analysis. In the validation cohort, rs7965281 was tested for association with each of the severity scores. There was no association with the inflammatory or the vaso-occlusive severity score but a trend towards association with the overall severity score (p= 0.08). All the SNPs were tested for association with the variable, number of hospitalizations for pain using regression analysis. Two additional SNPs, rs7855881 and rs34312136 were found to be nominally significant (p=0.01 and p=0.04 respectively). Rs7965281 shows a trend as well with p=0.06. In the literature, rs7965281 is associated with reduced risk for cutaneous melanoma in a large population based study as well as with blood pressure in a British population. Further work in our validation cohort, including MDR analysis for gene-gene interaction using the 3 significant SNPs remains to be done and this may provide further direction in future research. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq

Anemia ◽

10.1155/2015/195469 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Zeina A. Salman ◽

Meaad K. Hassan

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Readmission Rate ◽

Length Of Hospital Stay ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Opioid Use ◽

Asthma Symptoms ◽

The Mean ◽

High Readmission Rate

Objectives. Despite improvements in the management of sickle cell disease (SCD), many patients still experience disease-related complications requiring hospitalizations. The objectives of this study were to identify causes of hospitalization among these patients and factors associated with the length of hospital stay (LOS) and readmission.Methods. Data from 160 patients (<14 years old) with SCD who were admitted to the Basra Maternity and Children’s Hospital from the first of January 2012 through July 2012 were analyzed.Results. The main causes of hospitalization were acute painful crises (73.84%), infections (9.28%), acute chest syndrome (8.02%), and acute splenic sequestration crisis (6.32%). The mean LOS was4.34±2.85days. The LOS for patients on hydroxyurea (3.41±2.64days) was shorter than that for patients who were not (4.59±2.86days),P<0.05. The readmission rate (23.1%) was significantly higher among patients with frequent hospitalizations in the previous year (OR 9.352, 95% CI 2.011–43.49), asthma symptoms (OR 4.225, 95% CI 1.125–15.862), and opioid use (OR 6.588, 95% CI 1.104–30.336). Patients on hydroxyurea were less likely to be readmitted (OR 0.082, 95% CI 0.10–0.663).Conclusions. There is a relatively high readmission rate among patients with SCD in Basra. The use of hydroxyurea significantly decreases the LOS and readmission rate.

Download Full-text

Age-related prescription medication utilization for the management of sickle cell disease among Texas Medicaid patients

Journal of Opioid Management ◽

10.5055/jom.2021.0662 ◽

2021 ◽

Vol 17 (4) ◽

pp. 301-310

Author(s):

Nidhi Shukla, MS, MBA ◽

Jamie C. Barner, PhD, FAACP, FAPhA ◽

Kenneth A. Lawson, PhD, FAPhA ◽

Karen L. Rascati, PhD

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Age Groups ◽

Dual Therapy ◽

Cell Disease ◽

Opioid Use ◽

Medication Utilization ◽

Age Related ◽

Nonopioid Analgesics ◽

Chi Square Analysis

Introduction: Sickle cell disease (SCD) is associated with recurrent complications and healthcare burden. Although SCD management guidelines differ based on age groups, little is known regarding actual utilization of preventative (hydroxyurea) and palliative therapies (opioid and nonopioid analgesics) to manage complications. This study assessed whether there were age-related differences in SCD index therapy type and SCD-related medication utilization.Design and patients: Texas Medicaid prescription claims from September 1, 2011 to August 31, 2016 were retrospectively analyzed for SCD patients aged 2-63 years who received one or more SCD-related medications (hydroxyurea, opioid, or nonopioid analgesics).Outcome measures: The primary outcomes were SCD index drug type and medication utilization: hydroxyurea adherence, and days’ supply of opioid, and nonopioid analgesics. Chi-square, analysis of variance, and Kruskal–Wallis tests were used.Results: Index therapy percentages for included patients (N = 2,339) were the following: opioids (45.7 percent), nonopioids (36.6 percent), dual therapy-opioids and nonopioids (11.2 percent), and hydroxyurea (6.5 percent), and they differed by age-groups (χ2 = 243.0, p 0.0001). Hydroxyurea as index therapy was higher among children (2-12:9.1 percent) compared to adults (26-40:3.7 percent; 41-63:2.9 percent). Opioids as index therapy were higher among adults (18-25:48.0 percent; 26-40:54.9 percent; 41-63:65.2 percent) compared to children (2-12:36.6 percent). Mean hydroxyurea adherence was higher (p 0.0001) for younger ages, and opioid days’ supply was higher for older ages.Conclusions: Texas Medicaid SCD patients had low hydroxyurea utilization and adherence across all age groups. Interventions to increase the use of hydroxyurea and newer preventative therapies could result in better management of SCDrelated complications and reduce the frequency of pain crises, which may reduce the need for opioid use.

Download Full-text

Medical marijuana certification for patients with sickle cell disease: a report of a single center experience

Blood Advances ◽

10.1182/bloodadvances.2020002325 ◽

2020 ◽

Vol 4 (16) ◽

pp. 3814-3821 ◽

Cited By ~ 1

Author(s):

Susanna A. Curtis ◽

Dana Lew ◽

Jonathan Spodick ◽

Jeanne E. Hendrickson ◽

Caterina P. Minniti ◽

...

Keyword(s):

Health Care ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Medical Marijuana ◽

Care Utilization ◽

Cell Disease ◽

Opioid Use ◽

Admission Rates ◽

Single Center Experience ◽

Few Data

Abstract More than one-third of adults with sickle cell disease (SCD) report using cannabis-based products. Many states list SCD or pain as qualifying conditions for medical marijuana, but there are few data to guide practitioners whether or whom should be certified. We postulated that certifying SCD patients may lead to a reduction in opioid use and/or health care utilization. Furthermore, we sought to identify clinical characteristics of patients who would request this intervention. Retrospective data obtained over the study period included rates of health care and opioid utilization for 6 months before certification and after certification. Patients who were certified but failed to obtain medical marijuana were compared with those who obtained it. Patients who were certified were invited to participate in a survey regarding their reasons for and thoughts on certification. Patients who were certified for medical marijuana were compared with 25 random patients who did not request certification. Fifty adults with SCD were certified for medical marijuana and 29 obtained it. Patients who obtained medical marijuana experienced a decrease in admission rates compared with those who did not and increased use of edible cannabis products. Neither group had changes in opioid use. Patients who were certified for medical marijuana had higher rates of baseline opioid use and illicit cannabis use compared with those who did not request certification. Most patients with SCD who requested medical marijuana were already using cannabis illicitly. Obtaining medical marijuana decreased inpatient hospitalizations.

Download Full-text

A comment on pattern of opioid use in sickle cell disease

American Journal of Hematology ◽

10.1002/ajh.24643 ◽

2017 ◽

Vol 92 (4) ◽

pp. E42-E43 ◽

Cited By ~ 1

Author(s):

Xiulu Ruan ◽

Hong Wu ◽

Dian Wang

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Opioid Use

Download Full-text

Identification of Thrombospondin-1 and L-Selectin as Potential Plasma Biomarkers of Silent Cerebral Infarct In Children with Sickle Cell Disease Using a Proteomic-Based Approach

Blood ◽

10.1182/blood.v116.21.259.259 ◽

2010 ◽

Vol 116 (21) ◽

pp. 259-259

Author(s):

Lisa M. Williams ◽

Zongming Fu ◽

Pratima Dulloor ◽

Kun Yan ◽

John J. Strouse ◽

...

Keyword(s):

Blood Pressure ◽

African American ◽

Sickle Cell Disease ◽

Systolic Blood Pressure ◽

Sickle Cell ◽

Vascular Endothelium ◽

Validation Cohort ◽

Plasma Samples ◽

Cell Disease ◽

Control Subjects

Abstract Abstract 259 Objectives: Silent cerebral infarction (SCI) occurs in approximately 27% of children with sickle cell disease (SCD) by age 6 years, and is associated with decreased neurocognitive function and a 14-fold increased risk of progression to overt stroke. While several clinical parameters, such as increased white blood cell (WBC) and platelet counts and decreased hemoglobin (Hb) or hematocrit, have been reported in the literature to be associated with SCI, to date no validated biomarkers exist to predict SCI in patients with SCD. Furthermore, recent unpublished data from the Silent Infarct Transfusion (SIT) Trial has identified systolic blood pressure and total hemoglobin as risk factors. The aim of this study was to identify candidate biomarker plasma proteins that correlate with SCI in patients with SCD. Methods: We used a proteomic discovery approach involving three sequential separation steps to compare the plasma proteomes of 15 children with SCD (7 with SCI and 8 without SCI), aged 5–15 years. Baseline steady-state plasma samples were obtained from the SIT Trial Biologic Repository and matched for age, Hb and WBC. Plasma samples were Hb depleted in the first dimension, separated using immunoaffinity depletion and reverse phase liquid chromatography fractionation, and then trypsin-digested for characterization using label-free quantification on a LTQ-Orbitrap (Thermo) mass spectrometer. The resulting MS/MS data were analyzed using PASS (Integrated Analysis, Bethesda, MD) with X! Tandem searches (www.thegpm.org; version 2008.12.01) of the International Protein Index peptide database (human, 3.19). We measured candidate proteins in a validation cohort of 116 children with SCD (n=65 SCI, 51 non-SCI) and 24 age-matched, healthy African American control subjects using enzyme-linked immunosorbent assays (thrombospondin 1 [TSP1], L-selectin, RandD Systems, Minneapolis, MN) and immunoassays (E- and P-selectin, Mesoscale Discovery, Maryland). All samples were run in duplicate according to the manufacturers' protocols. Statistical differences in biomarker plasma concentrations between groups were compared by the Mann-Whitney U test. Results: TSP1 (5 peptides) and L-selectin (3 peptides) were among 335 proteins that showed differential detection between the SCI and non-SCI groups based on the spectral counts. TSP1 is an extracellular matrix glycoprotein that is involved with platelet aggregation, inhibition of neovascularization and tumorigenesis and has been shown to promote the adherence of sickle erythrocytes to the vascular endothelium. L-selectin is an adhesion molecule that mediates leukocyte interaction with the vascular endothelium. In a validation cohort of 116 children with SCD (n=65 SCI, 51 non-SCI) and 24 age matched, healthy African American control subjects, TSP1 and L-selectin were both significantly increased in SCI vs. non-SCI groups (median 8.5 vs. 6.2 μ g/ml for TSP1, P =0.03; 1.5 vs. 1.4 μ g/ml for L-selectin, P =0.03). As expected, neither TSP nor L-selectin were elevated in the age-matched normal controls (median=4.6 μ g/ml for TSP1, P =0.10, 1.2 μ g/ml for L-selectin, P =0.10). The specificity of the L-selectin results was verified by demonstrating that E-selectin and P-selectin were not increased in the SCI group. TSP1 was correlated with baseline oxygen saturation in both the SCI and non-SCI groups (r=-0.51, and r=-0.35, P<0.001). L-selectin correlated with systolic blood pressure in the SCI group only (r=0.3, P<0.02). Conclusions: TSP1 and L-selectin may represent the first two plasma biomarkers of SCI in children with SCD. Although further studies are needed, these and other potential biomarkers may provide insight into the pathophysiology of SCI, and may fill an important clinical need in identifying children with SCD who are at risk for SCI. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Pain and disease severity relate to long versus short-acting opioid use in adults with sickle cell disease: the PiSCES project

Journal of Pain ◽

10.1016/j.jpain.2012.01.067 ◽

2012 ◽

Vol 13 (4) ◽

pp. S15

Author(s):

W. Smith ◽

D. McClish ◽

B. Dahman ◽

J. Levenson ◽

I. Aisiku ◽

...

Keyword(s):

Sickle Cell Disease ◽

Disease Severity ◽

Sickle Cell ◽

Cell Disease ◽

Opioid Use ◽

Short Acting

Download Full-text

Clinical and Laboratory Predictors of 30-Day Hospital Readmission Risk in Adult Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2018-99-115248 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2384-2384

Author(s):

Seyed Mehdi Nouraie ◽

Melissa Saul ◽

Enrico M Novelli ◽

Gregory J. Kato ◽

Mark T Gladwin

Keyword(s):

Health Care ◽

Liver Disease ◽

Sickle Cell Disease ◽

Blood Transfusion ◽

Hospital Stay ◽

Sickle Cell ◽

Hospital Readmission ◽

Adult Patients ◽

Cell Disease ◽

Readmission Risk

Abstract Introduction: Thirty-day readmission risk is widely accepted as an indicator of quality of care. Sickle cell disease (SCD) has one the highest hospital readmission risk with a wide variation between different studies. In recent studies, older age, insurance status, and systemic complications including sepsis, renal and liver disease increased the risk of readmission whereas blood transfusion reduced the risk. During hospital stay, patients experience a variety of changes in their symptoms and laboratory measures. Evidence on the role of these changes on readmission risk is limited. In the current study, we aimed to assess the clinical and laboratory predictors of 30-day readmission risk in SCD adult patients in a tertiary health care system. Methods: Medical record discharge abstract files which cover visits for the SCD patients at the University of Pittsburgh Medical Center (UPMC) were extracted from electronic health records. Laboratory test results were obtained for each admission and were linked to discharge data. For each admission ICD 9/10 codes were used to identify the comorbidities. Blood transfusion information was recorded during each the admission. Natural language processing was used to extract medical concepts from chest X-ray and CT scan reports during patient's admission. Acute chest syndrome/pneumonia were identified from a combination of ICD codes and radiologic reports. For each laboratory value, a single rate of change (trajectory) was calculated with a random coefficient model from any measures during the hospital stay. Rate of changes were categorized to negative and positive trajectory. We used Generalized Estimating Equations models to assess predictors of 30-day readmission risk including the relationship between negative trajectory of any laboratory values duration the admission. Results: During January 2010 to May 2016, data for 2,108 hospital admissions in 173 SCD unique adult patients (median age of 32, 57% female and 59% SS genotype) were extracted. Risk of 30-day readmission was 41.2%. Older age (P <0.001) but not genotype (P = 0.8) predicted a lower readmission risk. Blood transfusion reduced readmission risk by 15% (Figure a). This effect was more significant in younger age (P for interaction with age = 0.045, Figure b). The most common discharge diagnoses were chronic pulmonary heart disease (23%), acute chest/pneumonia (22%), chronic renal disease (12%) and chronic liver disease (7%). Trajectory of neutrophil and WBC count changes were negative in 85% and 78% of admissions, respectively. These values were 67% for hemoglobin, 71% for creatinine and 46% for platelet count. During the period of hospital stay, decline in WBC (OR = 0.47, P = 0.030), neutrophil count (OR = 0.37, P = 0.023) or creatinine (OR = 0.40, P = 0.004) was associated with lower readmission risk. Conclusions: These results support that cardiopulmonary comorbidities are unexpectedly common in adult SCD patients. Blood transfusion in younger SCD patient reduced the readmission risk. Renal complications and leukocytosis in these patients contributed to health care utilization. Using advanced predictive models can help us to define patients who are at higher risk of readmission and generate strategies to reduce hospital readmission. Disclosures No relevant conflicts of interest to declare.

Download Full-text