Social Vulnerability Is Associated with Emergency Department Dependency in Pediatric Sickle Cell Disease Patients

Background: Sickle cell disease (SCD) is a complex genetic disorder characterized by significant, largely unpredictable heterogeneity in disease severity and healthcare utilization. The contribution of socioeconomic status (SES) and other environmental factors to this heterogeneity is poorly understood. In other disorders, SES is a major influence on healthcare quality and access, which can be affected by financial status, social stability, transportation, household overcrowding, and other variables. The multiplicative nature of these factors limits the ability to incorporate them in a single measure. The Social Vulnerability Index (SVI) was created by CDC to assist disaster management officials in identifying the locations of their most socially vulnerable populations (https://svi.cdc.gov/). SVI combines many of the SES factors that may contribute to disease severity and healthcare utilization. SVI has previously been validated for use assessing chronic conditions such as asthma, youth inactivity, and BMI. Thus, we hypothesized that SVI is associated with SCD-related severity and utilization. This analysis explores the relationship between census tract level social vulnerability and healthcare utilization in pediatric SCD patients. Methods: The Children's Healthcare of Atlanta's (CHOA) SCD Clinical Database houses a large, population-based cohort of pediatric sickle cell patients. It includes laboratory-confirmed SCD genotype, treatment history, and healthcare utilization for over 3,500 patients from 2010-2018. The database was queried for patients who had ≥1 SCD-related healthcare encounter from 2016-2018 and whose most recent address was in a metro Atlanta county. Addresses were geocoded and matched to CDC's SVI at the census tract level. The SVI combines 15 measures from the US Census and groups them into four related themes - SES, Household Composition & Disability, Minority Status & Language, and Housing & Transportation , which are combined into a percentile ranking of overall social vulnerability ranging from 0 (lowest) to 1 (highest). Patients were categorized by sickle cell anemia (SCA) genotypes (SS or Sβ0 Thalassemia) vs. other. Healthcare utilization was used to calculate the emergency department dependency ratio (EDR, ratio of ED visits to sum of ED and SCD clinic visits) and total inpatient days for acute illness as a measure of disease severity. As reported in previous studies, EDR was classified as high (>=0.33) or low (<0.33). SVI, age, and annual inpatient days were included as continuous variables. A logistic regression model was used to assess the relationship between SVI and EDR. SCA vs. other SCD genotypes, age, and total inpatient days were included as covariates and a backwards selection was used to find the best model. Results: Of the 2,578 active patients from 2016 to 2018, 1,328 met inclusion criteria. Mean age at the end of each measurement year was 10.0 years (SD=5.6), 47.7% were female, and 62.0% had SCA genotypes. Average inpatient days was 3.2 (SD=8.3). Average SVI was 0.50 (SD=0.28) and average EDR was 0.29 (SD=0.29); 44.8% of which were classified as high. All covariates were significant in the multivariate model. In the crude model, SVI was significantly associated with high EDR (OR=2.08, 95% CI: 1.62, 2.66). After controlling for inpatient length of stay, age, and genotype, SVI remained positively associated with high EDR (OR=1.85, 95% CI: 1.41, 2.44). Of the covariates, total hospital days (OR=1.28, 95% CI: 1.25, 1.32) was associated with a higher EDR. Older age (OR=0.97, 95% CI (0.96, 0.99) and SCA genotype (OR=0.41, 95% CI: 0.35-0.48), were negatively associated with high EDR. After controlling for SCA genotype, age, and length of stay, a 1 unit increase in SVI was associated with 85% greater odds of having a high EDR. Conclusions: The analysis demonstrates a significant relationship between SVI and EDR. Further analyses will assess the effect of distance to emergency department, treatment with hydroxyurea or chronic transfusions, and individual themes within SVI to further elucidate this relationship. A limitation of this analysis is that encounters were limited to those occurring at a CHOA facility. Overall, the results support our hypothesis that high social vulnerability is associated with increased reliance on the emergency department for care and that SVI may be a predictor of disease severity and increased healthcare utilization. Disclosures Lane: NHLBI: Research Funding; CDC: Research Funding; GA Dept: Other: Contract for newborn screeninjg follow-up services services; Bio Products Laboratory: Other: Sickle Cell Advisory Board; FORMA Therapeutics: Other: Clinical Advisory Board.

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Effects of BCL11A Shmir-Induced Post-Transcriptional Silencing on Distributions of HbF in Single-RBCs and Reticulocytes

Blood ◽

10.1182/blood-2021-150186 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 967-967

Author(s):

Nicolas Hebert ◽

Erica B. Esrick ◽

Myriam Armant ◽

Christian Brendel ◽

Marioara Felicia Ciuculescu ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Insertion Site ◽

Fetal Hemoglobin ◽

Fold Increase ◽

Advisory Board ◽

Cell Disease ◽

Advisory Committees

Abstract NH and EE equally contributed. ADW and PB co-signed. The expression of fetal hemoglobin (HbF) is one of the main targets of sickle cell disease treatment, as it inhibits the polymerization of hemoglobin S. The hypothesis of an inhibitory threshold of HbF per red blood cell (RBC) has been suggested, 1 although not well defined, as the overall percentage of HbF does not reflect the heterogeneous distribution of HbF per cell. Likewise, the qualitative analysis of RBCs containing HbF, called F cells, is neither reproducible nor clinically interpretable, due to low expression. 2 We have developed a technique for measuring the amount of HbF per cell, to determine thresholds of HbF expression per RBC correlated with clinical and biological effects. 2 Among genes controlling its expression, BCL11A has a major repressive effect on the expression of gamma globin/HbF during the fetal to adult hemoglobin switch. Post-transcriptional silencing of BCL11A, using lentivirus expression of a shRNA embedded in a microRNA architecture (shmiR) to re-activate γ-globin expression, is safe and demonstrates high levels of %HbF in a pilot clinical study (NCT 03282656). 3 Here, we show the quantitative measurement of HbF per RBC and reticulocyte. Methods: During patient follow-up, HbF quantification per single cell RBC was performed using a fluorescent HbF antibody. 2 Addition of an anti-CD71 fluorescent antibody allowed selection of reticulocyte sub-populations for determining their HbF content. Fold-increase in percentage of RBC versus percentage of reticulocyte were calculated. Kinetics of HbF/RBC and HbF/Reticulocyte were modeled using mixed effects polynomial linear regression to account for the correlation between repeated data over time. Results: With a median follow-up of 15 months [12-20] after gene transfer, figure 1 shows the mathematical modeling of single-RBC HbF measurement representing RBC percentage containing at least 2, 4, 6, 8 and 10 pg of HbF. Percentage of RBC above each threshold was higher compared to 14 hydroxyurea treated patients for 6 months. Figure 2 shows fold increase between reticulocytes and RBCs with same thresholds of HbF/cell. For low thresholds, RBCs were found in same percentage as reticulocytes whereas RBCs containing increasing levels of HbF were found in higher percentage than reticulocytes, until 6pg/cell showing a clear selective advantage for red cells with a threshold ≥ 6pg/cell of HbF. Figure 3 shows different kinetics of HbF increase according to two different transduction strategies with 2 enhancers in patients 2-4 compared to one enhancer in patients 6-8. Conclusion: BCL11A down-regulation in six clinical trial subjects was associated with an in vivo selection process RBCs with ≥ 6pg HbF per cell attained with different engraftment kinetics, depending on transduction processes, and ultimately stable high level and broadly distributed HbF. 1 Steinberg MH, Chui DH, Dover GJ, Sebastiani P, Alsultan A. Fetal hemoglobin in sickle cell anemia: a glass half full? Blood. 2014 Jan 23;123(4):481-5. 2 Hebert N, Rakotoson MG, Bodivit G, et al. Individual red blood cell fetal hemoglobin quantification allows to determine protective thresholds in sickle cell disease. Am. J. Hematol. 3 Esrick EB, Lehmann LE, Biffi A, et al. Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease. N. Engl. J. Med. 2021;384(3):205-215. Figure 1 Figure 1. Disclosures Esrick: bluebird bio: Consultancy. Audureau: GBT: Honoraria. Higgins: Sebia, Inc.: Honoraria; Danaher Diagnostics: Consultancy. Williams: BioMarin: Membership on an entity's Board of Directors or advisory committees, Other: Insertion Site Advisory Board; Geneception: Membership on an entity's Board of Directors or advisory committees, Other: Scientific Advisory Board; Emerging Therapy Solutions: Membership on an entity's Board of Directors or advisory committees, Other: Chief Scientific Chair; Beam Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Scientific Advisory Board; Alerion Biosciences: Other: Co-founder (now licensed to Avro Bio, potential for future milestones/royalties); Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Novartis ETB115E2201 (eltrombopag in aplastic anemia). Advisory fees donated to NAPAAC.; Orchard Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Membership on a safety advisory board (SAB): SAB position ended 05/20/2021. Co-founder , Patents & Royalties: Potential for future royalty/milestone income, X-SCID. Provided GMP vector for clinical trial, Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Other: Insertion Site Analysis Advisory Board, Patents & Royalties: BCH licensed certain IP relevant to hemoglobinopathies to bluebird bio. The current license includes the potential for future royalty/milestone income. Bluebird has indicated they will not pursue this as a clinical program and BCH is negotiating return of, Research Funding. Bartolucci: AGIOS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Jazz Pharma: Other: Lecture fees; Emmaus: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding; INNOVHEM: Other: Co-founder; Hemanext: Consultancy; GBT: Consultancy; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; Fabre Foundation: Research Funding.

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Health Literacy, Self-Efficacy and Knowledge of Sickle Cell Disease Among Caregivers

Blood ◽

10.1182/blood-2019-129888 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4841-4841

Author(s):

Maite E. Houwing ◽

Rowena Grohssteiner ◽

Sonja A.M.C. Teuben ◽

Jan A Hazelzet ◽

Anne P.J. de Pagter ◽

...

Keyword(s):

Health Literacy ◽

The Netherlands ◽

Health Information ◽

Sickle Cell ◽

Self Efficacy ◽

Research Funding ◽

Healthcare Professionals ◽

Cell Disease ◽

Lower Education ◽

The Relationship

Introduction Sickle cell disease (SCD) is a hereditary red blood cell disorder characterized by severe anemia, acute and painful vaso-occlusive crises and progressive organ failure. Success of health management of children with SCD is highly contingent on caregivers' capabilities. Caregivers of SCD affected children must perform a variety of tasks including communication with healthcare providers, reading and understanding of health information, interpretation of acute symptoms and administration of medication and complex decision making with regard to treatment options. A construct which describes the knowledge and competences of persons to meet the complex demands of health is 'health literacy' (HL) (1, 2). The measurement and assessment of HL is of growing importance due to expected and reported relationships between inadequate HL and health outcomes (3-5). In addition, caregivers with higher HL levels feel more confident in their ability to perform caregiving tasks, e.g. have a higher self-efficacy, often associated with higher quality of life (6, 7). Information on literacy levels and the relationship between HL, disease knowledge and self-efficacy may guide interventions in comprehensive SCD care. The aims of this study were to: (a) gain insight into levels of HL in caregivers of children with SCD using objective and subjective measures and to (b) assess the relationship between HL, caregivers self-efficacy' in communication with healthcare professionals and knowledge of SCD on different topics related to the illness. This abstract reports preliminary results. Methods In this cross-sectional, observational study, we included caregivers of children with SCD who attended the outpatient clinic of the Sickle Cell Comprehensive Care Center in the Erasmus Medical Center for a routine follow-up visit. Caregivers included in the study had to be able to communicate verbally in Dutch with professionals. HL was measured using the Short Assessment of Health Literacy in Dutch (SAHL-D) (8, 9); self-reported HL was evaluated by the Set of Brief Screening Questions (SBSQ) (10, 11). Self-efficacy was measured using the Perceived Self-Efficacy in Caregiver-Patient Interactions (PECPI) scale (12). Knowledge of SCD was assessed using a structured 13-item questionnaire (SCD-K) based on information and education provided in our clinic. Since data were not-normally distributed, they were analyzed using non-parametric statistics. Results To date, a total of 42 caregivers were included. Study inclusion will continue until at least 75 caregivers have been included. Demographics are presented in Table 1. Caregivers were mainly the child's mother (81.0%) often the single head of household (66.7%). The mean age of caregivers was 34.4 years. Educational level ranged from never attended school to post college Almost a quarter (23.8%) of caregivers was born in the Netherlands, others the rest were non-western migrants (76.2%). 78.6% of caregivers had low HL according to the SAHL-D. Caregivers with lower HL were more likely to have lower education (p=0.012) and to have been born outside the Netherlands (p=0.002). Only four caregivers (9.5%) reported having difficulties in understanding and applying health information (measured by SBSQ). The correlation between the SAHL-D and the SBSQ scores was weak (r=0.39). Mean scores on the SBSQ and PECPI were high, indicating that caregivers perceived their abilities for self-efficacy and their ability to read and understand medical information as quite high. Responses to individual SCD-K items however suggest large knowledge deficits: only 64.3% of caregivers knew which temperature is considered as fever [>38.0 °C or >38.5 °C] and only 14.3% was aware which risk factors are able to provoke sickle cell crises. The relationship between literacy status and item responses on SCD-K assessment scale was also examined. Caregivers with low literacy scored significantly lower on almost every individual item. Discussion Inadequate HL is highly prevalent in caregivers of children with SCD. Not being born in the Netherlands and lower education levels are strong predictors of low HL. Our study suggests that healthcare professionals should be attentive to possible low HL. In addition, these results underline that health information should be tailored to the HL skills and specific context of patients and their families. Disclosures Cnossen: NWO: Other: Governmental grants , ZonMW, Innovation fund and Nationale Wetenschapsagenda 2018; Roche: Other: Travel Grants; Takeda: Other: Travel Grants, Research Funding; Shire: Other: Travel Grants, Research Funding; Baxter: Other: Travel Grants, Research Funding; Sobi: Research Funding; CSL Behring: Other: Travel Grants, Research Funding; Nordic Pharma: Research Funding; Novo Nordisk: Research Funding; Pfizer: Other: Travel Grants, Research Funding; Bayer: Other: Travel Grants, Research Funding.

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Neurocognitive Impairment Predicts Poor Transition Outcomes Among Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2019-121617 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 519-519

Author(s):

Anjelica C. Saulsberry ◽

Marita Partanen ◽

Jerlym S. Porter ◽

Pradeep S. B. Podila ◽

Jason R. Hodges ◽

...

Keyword(s):

Gene Therapy ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Clinical Development ◽

Cell Disease ◽

Adult Care ◽

Transition Outcomes ◽

Ambulatory Services ◽

The Relationship

Introduction: In the United States, most children with sickle cell disease (SCD) survive into adulthood and transfer from pediatric to adult-centered care. Cognitive deficits begin during childhood and are highly prevalent among individuals with SCD, potentially affecting their functional ability to establish adult care and navigate the new adult care environment. Lack of engagement in adult care can place youth with SCD at higher risk for care discontinuity and higher disease morbidity and mortality. The relationship between cognition and transition to adult care has not been examined. We hypothesized that better performance on measures of neurocognition were associated with decreased latency in initiating adult care, greater retention in adult care, and increased utilization of adult ambulatory services. As a secondary objective, we examined the relationship of environmental outcomes to transition outcomes. Methods: We included participants enrolled in the Sickle Cell Research and Intervention Program (SCCRIP; Hankins J. et al, Pediatric Blood and Cancer 2018), a longitudinal lifetime cohort study of individuals with SCD that monitors neurocognition. Participants were included if they underwent neurocognitive screening assessment in adolescence, prior to their transfer to adult care and if they satisfied their first appointment in adult care. The neurocognitive screening battery included measures of estimated global intelligence (Wechsler Abbreviated Scales of Intelligence, 2nd Ed; WASI-2) and sustained attention (Continuous Performance Test, 2nd Ed; CPT-2). Environmental factors included the Economic Hardship Index (EHI), guardian employment status while in pediatric care, and the number of persons living in the household. Use of adult ambulatory services was measured by the number of outpatient visits per patient-year. The association between cognitive performance and the latency from pediatric to adult care, adult care retention and environmental variables was examined using the 2-sample t test if the data were normally distributed or the Wilcoxon rank-sum test otherwise. Categorical variables were analyzed with the Chi-square test or Fisher's exact test. Transition outcomes were also analyzed as continuous variables using univariate linear regression. All reported p-values are two-sided. Results: Eighty adolescents with SCD ages 15-18 years at the time of their cognitive assessment (58% male, 63% HbSS/HbSβ0-thalassemia) were included; most transferred <6 months from the last pediatric visit Table 1). Of these 80 patients, 61 and 43 had sufficient follow-up time to examine their retention in adult care 12 and 24 months after transfer, respectively. Fifty out of the 61 patients (82%) remained in adult care > 12 months, and 31 of the 43 (72%) remained in adult care >24 months after their first adult visit. Higher Full-Scale IQ was associated with establishing adult care ≤2 months from last pediatric visit (Table 1; Figure 1A, 1B). Belonging to families with fewer children, smaller households and a higher WASI-2 Verbal Comprehension Index were associated with establishing adult care ≤6 months from last pediatric visit. Better CPT-2 Commissions performance (less attention deficit) was associated with increased adult care retention at 12 and 24 months (Table 2; Figure 1C,1D). Having a working guardian was associated with less retention at 12 months (p=0.01), whereas having an unemployed primary guardian was associated with greater retention at 24 months (p=0.02). Further, an employed guardian was associated with greater utilization of adult ambulatory services (p=0.01). EHI was not significantly related to transition outcomes. No relationship was found between adult ambulatory services and neurocognitive assessment. Conclusion: Neurocognitive deficit (lower IQ and attention deficits) may decrease short and long-term engagement in adult care among youth with SCD as demonstrated by longer latency periods between pediatric and adult care and shorter adult care retention. Socio-economic factors may also play a role in transition outcomes but require further investigation. Investigation of disease modifying therapies that preserve cognitive function should be prioritized. Interventions that account for patients' cognitive level and their environment should be considered in the individualization of transition plans. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; Amphivena Therapeutics: Research Funding; Incyte: Consultancy; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; Cell Works: Consultancy; Bioline: Consultancy; Celgene: Consultancy; RiverVest: Consultancy; WUGEN: Equity Ownership. Wang:Agios Pharmaceuticals: Consultancy; Novartis: Consultancy. Zhao:MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Kang:MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Hankins:National Committee for Quality Assurance: Consultancy; NHLBI: Research Funding; Global Blood Therapeutics: Research Funding; Novartis: Research Funding; LYNKS Foundation: Research Funding; NHLBI: Honoraria; ASPHO: Honoraria; Bluebird Bio: Consultancy.

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Age-Related Emergency Department Reliance and Healthcare Resource Utilization in Patients with Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.475.475 ◽

2012 ◽

Vol 120 (21) ◽

pp. 475-475

Author(s):

Morey A. Blinder ◽

Francis Vekeman ◽

Medha Sasane ◽

Alex Trahey ◽

Carole Paley ◽

...

Keyword(s):

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Healthcare Costs ◽

Research Funding ◽

Transition Period ◽

Cell Disease ◽

Adult Care ◽

Age Related ◽

Ed Visits

Abstract Abstract 475 Introduction: For sickle cell disease (SCD) patients (pts), inadequate care during pediatric to adult transition may result in increased emergency department (ED) utilization. Emergency department reliance (EDR: total ED visits/total ambulatory [outpatient + ED] visits) identifies the proportion of ED visits in relation to all ambulatory visits and differentiates between acute episodic ED users from those who may not have adequate access to outpatient care. The aim of this study is to investigate age-related patterns of EDR and associated healthcare costs in pediatric SCD pts and those transitioning from pediatric to adult care. Methods: State Medicaid data from FL (1998–2009), NJ (1996–2009), MO (1997–2010), IA (1998–2010), and KS (2001–2009) were used for this study. Pts with ≥2 SCD diagnoses (ICD-9 282.6x) and ≥1 blood transfusion were included in the analysis. Pts were followed for as long as they were enrolled in Medicaid. Quarterly rates of outpatient visits, ED visits, EDR, SCD complications associated with ED visits, and ED visits resulting in hospitalization were evaluated. Total healthcare costs were calculated and stratified by outpatient (OP), inpatient (IP), ED, and prescription drug (Rx). SCD complications included pain, stroke, leg ulcers, avascular necrosis, infections, as well as pulmonary, renal, and cardiovascular events. Based on published thresholds, high EDR was defined as >0.33. A logistic regression model was used to assess associations between high EDR and transition age (<18 vs. ≥18 years [yrs]), transfusions, hydroxyurea use, and SCD complications. Other covariates included transfusions during the previous quarter, other relevant medications (e.g.: pain medication, diuretics, anticoagulants), comorbidities (e.g.: hypertension, myocardial infarction, liver disease), and, serving as proxies for overall health status, the frequency of OP, IP, and ED visits during the previous quarter. Regressions analyses were also used to calculate adjusted costs differences between pts with high vs. low EDR. Findings: A total of 3,208 pts were included (FL: 1,550, NJ: 992, MO: 489, KS: 121, IA: 56) in the study. Each pt was observed for an average (SD) of 6.0 (3.1) yrs. Average ED visits/quarter increased from 0.76 to 2.29 between age 15 and 24, reaching a peak of 2.9 at age 36 (Figure 1). Regardless of age, the most common SCD complications associated with ED visits were pain, infection, and pneumonia. Beginning at age 15, EDR rose from 0.17 to reach 0.29 at age 22, and remained high throughout adulthood. The quarterly rate of ED visits resulting in hospitalizations followed a similar pattern. Regression analysis indicated that pts were more likely to have high EDR during the post-transition period (≥18 yrs old, odds ratio [OR]: 2.38, p<0.001) and when experiencing an SCD complication (OR: 4.18, p<0.001). Pts with high EDR incurred statistically significantly higher inpatient and ED costs, resulting in significantly higher total costs (high vs. low EDR, unadjusted costs difference, OP: -$441, p<.001; IP: $7,427, p<.001; ED: $442, p<.001; Rx: -$447, p=0.182; total: $7,376, p<.001 [Table 1]; adjusted costs difference, OP: -$285; IP: $3,485; ED: $120; Rx: -$91; total: $3,086, p<.001 for all). Conclusion: Compared to children, pts transitioning to adulthood relied more on ED for their care. Moreover, pts with high EDR incurred more frequent hospitalizations and significantly higher healthcare costs, highlighting the need to improve transition related support including better access to primary care and increased engagement with SCD patients. Disclosures: Blinder: Novartis Pharmaceuticals: Consultancy, Research Funding. Vekeman:Novartis Pharmaceuticals: Research Funding. Sasane:Novartis Pharmaceuticals: Employment. Trahey:Novartis Pharmaceuticals: Research Funding. Paley:Novartis Pharmaceuticals: Employment. Magestro:Novartis Pharmaceuticals: Employment. Duh:Novartis Pharmaceuticals: Research Funding.

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Creatinine, Lactate Dehydrogenase, and C-Reactive Protein As Indicators of Acute Vaso-Occlusive Crisis and Sickle Cell Disease Severity in the Emergency Department

Blood ◽

10.1182/blood.v124.21.4940.4940 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4940-4940

Author(s):

Elena M James ◽

LaShon C Sturgis ◽

Abdullah Kutlar ◽

Robert Gibson ◽

Matthew L Lyon

Keyword(s):

Emergency Department ◽

Disease Severity ◽

Sickle Cell ◽

User Group ◽

Cell Disease ◽

C Reactive Protein ◽

High User ◽

Reactive Protein ◽

Hb S ◽

Ed Visits

Abstract Sickle cell disease (SCD) patients often seek care in the Emergency Department (ED) due to vaso-occlusive crisis (VOC), the most common complication of SCD. Currently, no diagnostic test can determine if a SCD patient is having an acute VOC. This study analyzed the utility of creatinine (Cr), C-reactive protein (CRP), and lactate dehydrogenase (LDH) as indicators of acute VOC and increased disease severity. We hypothesized that increased levels of these markers correlated with acute VOC and increased SCD severity because they are suggestive of renal injury, accelerated hemolysis, and inflammation with VOC onset. Data was collected from a cohort of 171 patients followed at an adult sickle cell clinic from 2005 to 2012. Eligibility criteria included a minimum age of 18 with SCD genotypes Hb S/S, Hb S/C, Hb S/B+, or Hb S/B0. Marker values were collected prospectively, with baseline values obtained during non-crisis visits to the sickle cell clinic, and crisis values obtained during treatment for VOC in the ED. Patients were categorized as high or low ED users to approximate disease severity using two methods. Aggregate (AG) analysis assigned patients to the high user group, 65 patients (38%), if they had >3 VOC ED visits in any year. The low user group, 106 patients (62%), had 3 or less VOC ED visits in any year. Since disease severity fluctuates in individual patients over time, a second analysis divided the groups using an individual (IN) analysis where high user-years were defined as >3 VOC ED visits/year. IN analysis resulted in 226 (47%) high user-years and 259 (53%) low user-years. Statistical analysis using R Version 3.1.0 compared overall average baseline and crisis values to determine if biomarker levels increased in acute VOC. High and low user values were compared with respect to baseline and crisis averages to determine if biomarker levels correlated with SCD severity. Analysis of baseline and crisis values over the study period evaluated changes with age. Statistical significance was set to p<0.05. Table 1 summarizes the significant results of the statistical analysis. Changes in Cr and LDH between high and low users with respect to baseline, crisis, and difference between baseline and crisis were not statistically significant in both analyses. However, crisis CRP values between high and low user-years differed significantly. In both analyses, overall baseline and crisis Cr and LDH differed significantly. Crisis Cr and baseline LDH increased significantly over the 7-year time span. Table 1 Marker Variable Mean SD P-value Cr (mg/dL) AG overall baseline 0.80 0.687 0.0053 AG overall crisis 1.08 1.55 IN overall baseline 0.817 0.931 0.0178 IN overall crisis 1.00 1.48 Overall crisis start 1.02 1.59 0.0087 Overall crisis end 1.10 1.76 LDH (U/L) AG overall baseline 387 196 7.90E-5 AG overall crisis 463 227 IN overall baseline 395 228 0.0194 IN overall crisis 445 269 Overall baseline start 373 181 0.0015 Overall baseline end 417 234 CRP (mg/dL) IN high user crisis 2.61 4.31 0.0247 IN low user crisis 1.05 1.02 Creatinine, a urinary muscle metabolite, is a marker of kidney function. Dehydration, a potential cause of VOC, may explain the rise in Cr during crisis. LDH increase in crisis reflects increased intravascular hemolysis during VOC. The results support the utility of Cr and LDH as indicators of acute VOC in the ED. However, both AG and IN analyses reveal no distinction between high and low users of the ED. LDH and Cr increase with age, suggesting potential for monitoring SCD disease progression. Increased Cr crisis levels with age may reflect kidney dysfunction due to medullary ischemia from multiple VOCs. Increased non-crisis LDH levels with age suggest increased disease severity, progressive organ damage, and steady state pro-inflammatory conditions. CRP, an acute phase reactant indicative of systemic inflammation, was higher during crisis in high user-years than in low user-years. The correlation of increased crisis CRP to increased ED usage may represent a higher inflammatory state in these patients. Further studies are needed to determine the cause and effect relationship of this correlation. The data supports the utility of Cr and LDH as markers for acute VOC. LDH and Cr also demonstrate potential as indicators of SCD disease severity in a long-term context, while CRP demonstrates potential to monitor for short-term inflammatory states leading to increased severity in frequency and possibly intensity of VOC. Disclosures No relevant conflicts of interest to declare.

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Episodic Patterns of High Emergency Department Utilization Among Sickle Cell Disease Patients

Blood ◽

10.1182/blood.v128.22.316.316 ◽

2016 ◽

Vol 128 (22) ◽

pp. 316-316

Author(s):

Susan Paulukonis ◽

Lisa Feuchtbaum ◽

Elliott Vichinsky ◽

Mary Hulihan

Keyword(s):

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Surveillance System ◽

Research Funding ◽

Cell Disease ◽

Ed Visits ◽

High Utilization ◽

The Mean ◽

Over Time

Abstract Background: High utilization of emergency department (ED) services among those with sickle cell disease (SCD) compared to the general population and compared to those with other chronic diseases is well documented in the literature. Some reports note that high utilization is episodic. Most analyses address the problem as a consistent one within patients, rather than consistent over time across the patient population but sporadic for patients. Reducing the high rate of ED utilization among patients with SCD requires an understanding of temporal patterns of ED utilization, the consistency of ED utilization over time by patients and the proportion of the population affected at any given time. Methods: CDC has developed the Sickle Cell Data Collection program (SCDC) to conduct state level surveillance in this disease, and to continue and improve upon work begun through the Registry and Surveillance System in Hemoglobinopathies (RuSH). Through SCDC, California has collected ED and hospitalization data for years 2005-2014 on 4,325 people with SCD. A period of high ED utilization among this cohort was defined as three or more ED encounters (either treat and release or admission to the hospital from the ED) for any diagnosis (not only SCD diagnoses) each fewer than 30 days from the prior visit. The start of an episode of high utilization is the date of the first ED encounter; the end is the date of the last eligible ED encounter. All cohort members were divided into categories of utilization using the proportion of time spent in periods of high utilization divided by the total time in cohort. Total time is cohort is defined as the length of time from the earliest appearance in the ED or hospital data 2005-2014 to the latest appearance. The five categories were defined as no episodes of high ED utilization, and approximate quartile groups for those with high ED utilization: 1.1 to 3.0%, 3.1-10.0%, 10.1% or greater. Age categories (pediatric is < 21 years, and adult is 21 years or older) are defined as patient age at close of study (end of 2014) or at death if prior. Patient ID beginning with P is a pediatric, A is adult in the figures. Results: There were 4,325 individuals with 27,694 person years in the cohort (mean 6.4 person years, median 7.6 person years). Sixty-three percent (n=2,715) of the cohort were aged 21 years and older. Forty-five percent, (n=1,955, 513 pediatric and 1,442 adults) had at least one episode of high utilization during the 10 year study for a total of 7,866 episodes of high utilization. Forty-three percent of patients with one or more high utilization episodes were male, and 63% were between the ages of 20 and 50. Nine percent of these high utilizing patients' total time in the cohort was made up of episodes of high utilization. The mean time span from start of episodes of high utilization to end of the episodes was 63.3 days, median 35 days; mean number of ED visits per episode was 9.0, median 4.0. Most episodes of high utilization were brief: 42.2% included just three visits, and 70.7% included five or fewer ED visits. Among these individuals with episodes of high utilization, the mean number of such episodes was 4.0 over the 10 years study period, and the median was 2.0. Most (76.4%) had five or fewer high utilization episodes, and 35.5% had just one (n = 693). Sample utilization patterns, including hospital admissions, are shown in Figure 1. Conclusions: We demonstrate that among individuals with SCD seen in a population-based, statewide surveillance system, periods of high ED utilization are common, but most SCD patients have only a limited number of short episodes of such utilization. We found that high ED utilization is episodic rather than consistent within individuals, and that while the range of time spent in episodes of high utilization varies, few patients are high utilizers of ED services over a long period of time. Statewide surveillance that follows individual patients over time and in different hospital settings and includes ED utilization (including visits not coded as being related to SCD), provides high quality public health information to inform clinicians and healthcare systems in their development of efforts to reduce ED utilization among those living with SCD. Figure 1 Figure 1. Disclosures Paulukonis: Pfizer: Research Funding; Biogen: Research Funding.

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The Effect of Individualized Pain Plans for Patients with Sickle Cell Disease on Emergency Provider Satisfaction: A Win for the Patient Can be a Win for the Provider

Blood ◽

10.1182/blood-2021-151771 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1889-1889

Author(s):

Sherraine Della-Moretta ◽

Rui Li ◽

David Way ◽

Michael G (MD) Purcell ◽

Melanie Heinlein ◽

...

Keyword(s):

Sickle Cell Disease ◽

Emergency Room ◽

Sickle Cell ◽

Research Funding ◽

Treatment Decision ◽

Treatment Decisions ◽

Cell Disease ◽

Satisfaction With Treatment ◽

Pain Crisis ◽

The Relationship

Abstract Background Sickle cell disease (SCD) is an inherited hematologic disorder that affects approximately 100,000 Americans and results in over 200,000 emergency departments visits annually, largely due to pain (Lanzkron et al). Delay in treatment in emergency room has been a significant barrier to patients with SCD, particularly adults. The objective of this study is to determine the effects of utilizing individualized pain plans for the treatment of vaso-occlusive crisis (VOC) on the satisfaction of healthcare providers in the emergency department (ED). Methods The Ohio State University has a comprehensive sickle cell center which creates individualized pain plans for patients who present to the ED with pain related to VOC. In January 2015, these pain plans were implemented into the electronic medical record listed in the overview of the problem sickle cell disease in each chart. In addition to creating pain plans, an interdisciplinary team was formed consisting of hematologists, pharmacists, and ED providers with the goal of education regarding SCD and the new implementation of pain plans. Surveys, using the secure web application, RedCAP, were distributed to the emergency department providers at the OSU ED. Questions included responders' role in the ED, prior experience with treating pain crisis, time to make treatment management decisions for VOC, satisfaction with treatment decision, and the providers view of their relationship with patients. Wilcoxon signed-rank test and Fisher's exact test were applied to evaluate the differences between pre and post survey numeric and categorical responses. Results Surveys were sent electronically to 170 ED providers. Sixty-nine responses, making up 40.5% of those surveyed, were obtained from 30 attending physicians, 2 fellows, 22 nurse practitioners or physician assistants, 1 registered nurse, and 14 residents. Of those who answered the survey, 14 had experience with treating pain crisis prior to the implementation of individualized pain plans. Implementation of individualized pain plans led to a reduction in median time to make treatment decisions from 5.5 to 2.5 minutes with a p-value of 0.0161. Provider satisfaction with treatment decisions improved as well (p = 0.0029) (Figure 2). In addition, ED providers felt more satisfied with their relationship with patients (p = 0.0078) (Figure 3). The majority of responders (91.2%) also rated their satisfaction with the treatment decision as either satisfied or very satisfied (Figure 1). Seventy eight percent of those answering the survey rated with relationship with patients as being good or very good (Figure 1). In terms of the ease of finding the pain plan in the electronic medical record, 91.3% of providers found them to be either very easy or easy to locate with 94.12% responding that implementing the plan was either easy or very easy (Figure 4). Regarding efficacy of the pain plans, 89.85% found the pain plans to be either effective or very effective (Figure 5). Finally, of the 36 providers who worked elsewhere, about half of the institutions from which they came did not have pain plans. Discussion The results of this study show the importance of utilizing individualized pain plans in the treatment of VOC in the ED. As shown in our prior studies, the implementation of individualized pain plans for patients with SCD resulted in a 48% decrease in time to first opioid in the ED, thereby signifying more prompt treatment (Della-Moretta et al). Not only does the data support an improvement in time to make treatment decisions, which benefit the patients, but providers also appear to view their use as an advantage. Pain plan utilization also leads to an increase in provider confidence in their treatment plans as well as a perceived improvement in patient-provider relationships. This is particularly significant as historically the relationship between emergency room staff and sickle cell patients has been seen as challenging by both patients as well emergency room providers (Haywood et al). Making patient centered individualized pain plans readily available, easily accessible, and simple to enact, can further enhance the relationship between the patient, emergency room, and the hematology team. Ongoing communication and education between all parties is beneficial. With the combination of patient and provider data, we show that a win for the patient can also be a win for the provider. Figure 1 Figure 1. Disclosures Desai: Pfizer: Other: Publication Fee, Research Funding; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy.

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Episodes of High Emergency Department Utilization Among a Cohort of Persons Living with Sickle Cell Disease

Blood ◽

10.1182/blood-2018-159 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 159-159

Author(s):

Susan T Paulukonis ◽

Eric Roberts ◽

Ron Brathwaite ◽

Ted Wun ◽

Mary M Hulihan

Keyword(s):

Health Care ◽

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Case Definition ◽

Inpatient Stay ◽

Cell Disease ◽

One Year

Abstract Introduction: Previous research has shown that persons living with sickle cell disease (SCD) are at risk for frequent emergency department (ED) encounters, either with or without an associated inpatient stay. The disease manifests as acute onset vaso-occlusive crises or other severe and unpredictable complications that require immediate care. However, day hospital or other appropriate care settings to manage these health care events are not available to most of the population with SCD. Previous observations suggest that-while ED usage is high overall for this population-this usage is also episodic, with periods of high use interspersed with relatively low usage. We here seek to characterize both high-use and quiescent periods among patients seen in California non-federal hospitals over a 12-year period. Methods: The California Sickle Cell Data Collection project is a statewide effort to use a wide range of administrative, clinical, and other data sources to describe the population living with SCD, their health outcomes, and health care utilization patterns. The data here include 2005-2016 inpatient encounters and ED encounters (with or without an associated inpatient stay) linked by patient identifiers across data set and year. A validated case definition that suggests a high probability of a true SCD 'case' was applied: three or more occurrences of a SCD specific International Classification of Disease Code (version 9 or 10, depending on the year) within any 5 year period between 2005-2016. Only patients who met this case definition and had one year or more of follow-up time in the cohort were included in these analyses. We tabulated the numbers of encounters (inpatient and ED) for each patient for non-overlapping 4-week periods and used Poisson mixture models to evaluate whether encounter frequency could be characterized as a mixture of one or more discrete distributions. Based on these findings, we examined the timing and duration of periods of ED utilization for patients over the course of the study. Quiescent periods are defined as lengths of time in which a person has zero or near zero encounters in ED or inpatient settings. Occasional and high use periods of ED utilization are defined quantitatively by the model (as below). Results: There were 5,090 patients meeting the case definition with one year or more of time in follow up. Patients were followed for a median of 9.8 years (range 1.0 to 11.0). There were 94,196 ED encounters without and 59,064 ED encounters with an associated inpatient stay. A 3-component model best combined predictive power, parsimony, and clinical relevance (Figure 1, upper left), including quiescent periods (mean 0.09 encounters; 88.8% of 4-week periods); occasional-use periods (mean 1.28encounters; 10.8% of 4-week periods); and high-use periods (mean 7.48 encounters; 0.5% of 4-week periods). All but two of the subjects experienced at least one quiescent period during the study, 75.9% experienced at least one occasional-use period, and 8.0% experienced at least one high-use period. Spells of occasional- or high-use lasted a median of 8 weeks regardless of patient age, and 3.6% of these included at least some very high-use. Median lengths of quiescent periods were 24 weeks for patients aged less than 20 years, 16 weeks for those 20 years of age and older. Examples of distribution of utilization over time by certain patients are shown in Figure 1, upper right and both lower panels. Conclusions: The majority of patients with sickle cell disease experience discrete periods during which ED and inpatient hospital encounters are not uncommon, separated by somewhat longer periods with few-to-no encounters. The experiences of -8.0% of patients further include periods during which encounters were very frequent. Patients aged 20 years and older are more likely to experience these high frequency episodes. Further research is planned to identify whether particular health related events or patient characteristics are associated with these high-utilization spells. Figure 1 Figure 1. Disclosures Paulukonis: Bioverativ Inc.: Research Funding; Pfizer Inc.: Research Funding; Global Blood Therapeutics Inc.: Research Funding.

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Association of Time to Initial Emergency Department Analgesia with Rate of Admission in Patients with Uncomplicated Sickle Cell Disease Vaso-Occlusive Crises

Blood ◽

10.1182/blood-2019-128496 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2307-2307

Author(s):

Andrew Schwartz ◽

Aaron Weingrad ◽

Ellen Dupont ◽

Maria R. Baer ◽

Jennie Y. Law ◽

...

Keyword(s):

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Subgroup Analysis ◽

Research Funding ◽

Admission Rate ◽

Shortness Of Breath ◽

Cell Disease ◽

Single Institution ◽

Dose Time

Introduction Painful vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). When the pain cannot be managed with home analgesics, patients often present to the Emergency Department (ED) in order to obtain relief. In the ED, the patient may encounter barriers to care that include provider bias, prolonged time to initial analgesic, and inadequate opioid dosing. The goal of this retrospective, single-institution study was to evaluate whether there was an association between the time to initial analgesic and the rate of admission for patients with SCD presenting with VOC. Methods A retrospective, single-institution chart review of adult ED visits between January 29, 2019 and June 30, 2019 was conducted for patients with a history of SCD who presented to the Adult ED for pain related to a VOC. Patients were divided into two cohorts: patients with a calculated door-to-dose time of ≤ 2 hours and patients with a door-to-dose time of > 2 hours. Registration time, time of first opioid administration, and disposition decision were recorded for each visit. The primary outcome of interest was to compare the rate of admission between the two cohorts. Results During the study period, 43 unique patients met the inclusion criteria. These patients were seen for a total of 264 visits for VOC-related acute pain. The overall rate of admission was 49% (130 of 264). The cohort of patients receiving analgesia within 2 hours included 75 (28% of total) subjects, whereas 189 (72%) patients received their first analgesic dose after 2 hours. The admission rate for patients with a door-to-dose time ≤ 2 hours was not significantly different from that for patients with a door-to-dose time > 2 hours (40% vs 53%, P = 0.076) A subgroup analysis was performed on patients presenting to the ED with uncomplicated VOC. This analysis excluded any visits in which patients presented for pain with additional complications (e.g. fever, chest pain, nausea/vomiting, shortness of breath). The purpose of this exclusion was to control for possible confounding by severity or complexity of illness, given that patients who have higher acuity are more likely to be seen faster, but also more likely to be admitted. A total of 47 patient visits from 23 unique patients were excluded from the total visits to perform the subgroup analysis. The most prevalent reasons for exclusion included URI (n=7), nausea and vomiting (n=7), shortness of breath (n=7), and fever (n=7). A subgroup of 37 patients was seen for a total of 217 visits for uncomplicated, VOC-related acute pain. The overall rate of admission was 46% (100 of 217). In 61 (28%) of the encounters analgesia was administered within 2 hours of registration, whereas in 156 (72%) of the encounters the first analgesic was received after 2 hours. In this subgroup of patients presenting with uncomplicated VOC, the admission rate for patients with a door-to-dose time ≤2 hours was significantly lower than that for patients with a door-to-dose time > 2 hours (33% vs 51%, P = 0.016). Conclusion For the entire cohort of patients with sickle cell disease, the administration of analgesia within 2 hours did not result in a statistically significant decrease in rate of admission. In the subgroup analysis, which excludes VOC-related pain visits with complications, the administration of analgesia within 2 hours did result in a statistically significant decrease in the rate of admission. This demonstrates the association between rapid administration of analgesia and a greater likelihood of discharge in the setting of uncomplicated VOC. Based on these preliminary findings, it would be reasonable to allocate additional resources to ensure the rapid administration of analgesia in patients with uncomplicated acute VOC pain crises. Disclosures Dupont: Pfizer: Other: Grant Support. Baer:Al Therapeutics: Research Funding; Incyte: Research Funding; Abbvie: Research Funding; Takeda: Research Funding; Kite: Research Funding; Forma: Research Funding; Astellas: Research Funding. Wilkerson:Pfizer: Other: Grant, Research Funding; Roche: Research Funding; Coaptech: Research Funding; Provay Pharmaceuticals: Research Funding; Cepheid: Other: Research Equipment; Janssen: Research Funding.

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Emergency Department Follow-up for Adults with Sickle Cell Disease.

Blood ◽

10.1182/blood.v114.22.241.241 ◽

2009 ◽

Vol 114 (22) ◽

pp. 241-241

Author(s):

Paula Tanabe ◽

John W Hafner ◽

Zoran Martinovich ◽

Elena Zvirbulis ◽

Ted Wun ◽

...

Keyword(s):

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Free Text ◽

Cell Disease ◽

Initial Interview ◽

Pain Scores ◽

Fund Research

Abstract Abstract 241 Study Objectives: To report the patients' ability to make and keep follow-up appointments, obtain analgesic prescriptions, and continued presence of pain for adult emergency department (ED) patients with sickle cell disease, seven and 30 days post ED visit. Barriers to making and keeping appointments and filling analgesic prescriptions were explored. Methods: A multi-center, prospective, longitudinal surveillance study enrolled patients from three academic medical centers (rural and urban). All ED patients ≥18 years with a chief complaint of a sickle cell pain episode were eligible for inclusion. Patients participated in an initial interview within 14 days of their ED visit and/or a second interview 21–37 days from their ED visit. Patients were interviewed at most once per month. The initial interview was conducted either during the hospitalization if admitted, or by follow-up phone call. The 2nd interview was conducted by phone. Pain scores at the time of both interviews were obtained. During the 2nd interview patients were asked if they were able to (1) make and keep a follow-up appointment, (2) whether or not they received and were able to fill an analgesic prescription and (3) associated barriers to either. Each study site conducted a minimum of 10 interviews per quarter. The study period was from October 2007 through July 2009. Descriptive statistics were used to report the data. A paired t-test was used to analyze differences in 7 and 30 day pain scores. Qualitative analysis was used to analyze free text barrier responses to making and keeping an appointment and filling prescriptions. Results: One hundred fifty seven initial interviews and 108 second interviews were completed, 80 different patients, 51% male, mean age 34±10, ages 18–51. Sixty six percent of patients reported they were able to obtain an appointment with a primary care physician after discharge. Of those with difficulty getting an appointment, barriers included: patient did not attempt to obtain an appointment (24%), no current appointments available (21%), difficulty getting a hold of MD office (18%), difficulty finding an MD (15%), no time to go to appointment (9%), lost MD phone number (6%), unspecified (6%), and no money for appointment (3%). Sixty six percent of patients with an appointment reported keeping their appointment or had a future appointment scheduled. Reasons why patients did not keep their appointment included: had to work, out of town, in hospital before appointment, forgot when appointment was, no money for appointment. At discharge from the ED or hospital, 70% of patients reported they needed an analgesic prescription and 66% of patients received a prescription for analgesics. Nineteen percent of patients reported difficulty filling their prescription. Difficulties included: prescription written incorrectly, dose was not available at pharmacy, pharmacy was closed, no money for prescription, homeless. Initial interview pain scores (median, IQR) were 7; (6.25, 8), and 2nd interview pain scores were 8; (7, 9). 57 patients participated in both an initial and follow-up interview and no differences in pain scores were reported, (p=0.83). Forty three percent of patients (who were discharged home from the ED) during the initial interview, and 59% of patients during the 2nd interview reported being unable to manage their pain at home. On the second interview, 74% of patients reported they were currently experiencing sickle cell pain and 72% reported they were taking pain medication every day. Conclusion Many ED patients did not keep follow-up appointments and a smaller number of patients experienced barriers to filling analgesic prescriptions. Over half of patients reported continued pain in the severe range 30 days after the ED visit. Disclosures: Tanabe: NIH, and Mayday Fund: Research Funding. Hafner:Mayday Fund: Research Funding. Martinovich:Mayday Fund: Research Funding. Zvirbulis:Mayday Fund: Research Funding. Artz:Mayday Fund: Research Funding.

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