Sickle Cell Disease Hospitalizations Research Articles

Impact of Pulmonary Hypertension on in-hospital outcomes amongst Sickle Cell Disease hospitalizations

Introduction: Pulmonary hypertension (PH) is a common and severe complication of Sickle Cell Disease (SCD), and an independent risk factor for mortality. While there is a clear association between SCD and PH, the predictors of PH in SCD and the impact of PH on in-hospital outcomes of SCD hospitalizations remains unknown. In our study, we sought to assess the in-hospital prevalence, predictors, and the impact of PH in SCD hospitalizations. Methods: We used the 2016 and 2017 National Inpatient Sample (NIS) to identify all adult hospitalizations with a primary discharge diagnosis of SCD. The sample was then stratified based on the presence or absence of PH. We used the Pearson chi-square test and weighted Student's t-test to analyze categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio for various clinical outcomes. SAS was used for the analysis, and the p-value was defined as <0.05. Results: We identified n=191,080 weighted hospitalizations for SCD, of which, 5.54% (n=10590) had concomitant PH. Female gender and comorbidities including hypertension, obesity, illicit drug use, hepatic cirrhosis, renal failure, prior venous-thromboembolism, valvular, and congenital heart disease were identified as significant predictors of PH in SCD. PH was associated with increased in-hospital mortality (1.04% vs 0.22%, AOR=2.14, 95% CI 1.15-3.98, p=0.0158). PH in SCD hospitalizations also increased the odds of - acute kidney injury (AKI), need for dialysis, acute respiratory failure (ARF), and need for mechanical ventilation for > 96 hours. The adjusted odds ratio for venous thromboembolism, shock-state, and the need for cardiac catheterization (both right and bilateral) were also higher in patients with PH. Overall hospitalization cost and length of stay increased (7.06±0.16 vs 1.82±0.02 days) in patients with SCD and PH (see table 1). Conclusion: In sickle cell disease hospitalizations, PH is independently associated with increased in-hospital morbidity and mortality, with an increased need for in-hospital catheterizations thereby, prolonging the length of stay and overall health care costs. Identifying and treating PH in the SCD population would improve in-hospital outcomes. Disclosures No relevant conflicts of interest to declare.

Sickle Cell Disease-Related Hospital Admissions and Acute Particulate Matter 2.5 Exposures

BackgroundFew studies have examined the impact of ambient air pollution exposures on sickle cell disease (SCD)- related hospital admissions. The findings of these studies have suggested potential relationships between SCD-related hospital admissions with acute exposures to ozone and particulate matter but the findings have been inconsistent. MethodsWe evaluated the association between acute exposure to ambient particulate matter 2.5 (PM2.5) air pollution and SCD-related hospital admissions among residents of South Carolina (SC). We obtained data on the first incident hospital admission between 2003 and 2006. PM2.5 exposures were estimated at the residential zip code level using spatio temporal statistical modeling. We used a semi-symmetric bidirectional case-crossover design to examine the association between hospital admissions and PM2.5 exposures 0 to 7 days prior to hospital admission (for the case period) and an equivalent 0 to 7 day control period within the same month, same days of the week. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAmong 1,937 individuals with at least one SCD hospital admission, the median age was 22 years, and the median percentage of persons living below poverty in the census tract of residence was about 16%. The average PM2.5 estimated exposure was about 10.1 ug/m3 on the day of hospital admission. The OR between admission and PM2.5 exposures on the day prior was 1.02 (95%CI: 1.00,1.03) while all other time windows examined hovered around 1.00 and were not statistically significant. ConclusionsWe observed some suggestion of increased risk for SCD-related hospital admission with an increase in PM2.5 exposures on the day prior to admission. However further investigation is needed to confirm these results.

The relationship of socio-environmental factors with hospital admissions and readmissions for Sickle Cell Disease

Background Though approximately 100,000 Americans have sickle cell disease (SCD), studies over long time periods and large geographic areas in the US are limited. Patients routinely have multiple hospital admissions per year. Identification of potential contributing socio-environmental factors is important to advance prevention efforts.Methods We conducted a descriptive study of SCD hospital encounters and readmissions by individual and area-level socio-environmental factors using representative encounter data from all hospitals in South Carolina. We obtained emergency department visit and hospital admission data from 2002 through 2013 for patients with a primary diagnosis related to SCD. We examined initial visits, total encounters, admission and readmission rates by individual and area-level socio-environmental factors.Results We identified 127,598 hospital encounters with complete data that were attributed to 6,631 individual patients. Average overall encounter rate was 19.2 (95% CI: 17.9, 20.6) and rate of readmissions within 30 days was 11.5 (95% CI: 10.2, 12.8). Encounter rates and readmission rates were lower among participants living in more affluent areas. Further, those who had Medicaid as their primary insurance had the highest rates of readmission.Conclusions We observed some suggestion of increased SCD-related hospital admission rates and readmissions among participants living in less affluent areas, thus prevention efforts may be warranted for these underserved communities.

S3101 Epidemiology of Clostridium difficile Infection in Sickle Cell Disease Population

INTRODUCTION: Patients with Sickle Cell Disease (SCD) are frequently hospitalized for vaso-occlusive crisis and are often given empirical antibiotic treatment which puts them at high risk for Clostridium Difficile (C. Diff) infection. There are no large studies which estimated the burden of C. Diff in SCD population. In our study, we used the nationally representative database to outline the trends and predictors of C. Diff among SCD patients. METHODS: We used National Inpatient Sample (NIS) for the years 2008-2017 by Healthcare Cost and Utilization Project. We extracted a study cohort of SCD hospitalizations using International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). C. Diff and other comorbidities were identified by ICD-9/10-CM codes and Elixhauser comorbidity software. Our primary objective was to delineate temporal trends, and predictors of C. Diff in SCD patients. We utilized Cochran Armitage trend test and multivariable survey logistic regression models to analyze the trends, predictors and outcomes. RESULTS: Out of a total 991,848 hospitalizations admitted with SCD, 5,182 (1.81%) hospitalizations were complicated with C. Diff infection. Incidence of C.Diff infection increased from 0.29% in 2008 to 0.55% in 2017 with a 6% yearly increase (OR 1.06; 95%CI 1.04-1.09 ;P < 0.001) (Figure 1). Patients who developed C.Diff infection had higher mean age (39 vs 33; P < 0.001), and more likely to be females (62% Vs. 38%,P < 0.001). Furthermore, in multivariable regression analysis, increasing age (OR 1.1; 95% CI 1.1-1.1; P < 0.0001), females (OR 1.2; 95% CI 1.1-1.4;P < 0.001), Septicemia (OR 3.6; 95% CI 3.0-4.3;P < 0.001) and Congestive Heart Failure (OR 1.3; CI 1.0-1.6; P < 0.0001) were associated with higher odds of C. Diff infection. Also comorbidities like Hypertension, Liver and Neurological Disorders were also associated with increased odds of developing C.Diff infection. Among the patients who developed C.Diff infection, 15% were discharged to long term facilities and 4% died during the hospitalization. Moreover C.Diff infection was also associated with higher Length of stay (11d Vs. 6d; P < 0.001). CONCLUSION: In this nationally representative study, we observed that incidence of C.Diff among SCD has been increasing over the last decade. We were also able to delineate several factors which were significantly associated with development of C.Diff infection which needs more in-depth studies to establish the causal relationship.Figure 1

Thrombin activation of PAR-1 contributes to microvascular stasis in mouse models of sickle cell disease

AbstractVaso-occlusive crisis (VOC) is the primary cause of morbidity and hospitalization in sickle cell disease (SCD); however, only 4 therapies (hydroxyurea, l-glutamine, crizanlizumab, and voxeletor) are currently approved in SCD. These agents limit the duration, severity, and frequency of crises. Activation of coagulation is a hallmark of SCD. Studies in animal models of SCD have shown that coagulation contributes to the chronic inflammation and end-organ damage associated with the disease; however, it is unknown whether coagulation directly contributes to the microvascular stasis that causes VOC. Herein, we demonstrate that inhibition of tissue factor (TF) and the downstream coagulation proteases factor Xa and thrombin significantly attenuates heme-induced microvascular stasis in mouse models of VOC. Pharmacologic inhibition of the principal thrombin receptor, protease activated receptor-1 (PAR-1), as well as deficiency of PAR-1 in all nonhematopoietic cells, also reduces stasis in sickle mice. PAR-1 deficiency was associated with reduced endothelial von Willebrand factor expression, which has been shown to mediate microvascular stasis. In addition, TF inhibition reduces lung vaso-occlusion in sickle mice mediated by arteriolar neutrophil-platelet microemboli. In sum, these results suggest that prophylactic anticoagulation might attenuate the incidence of VOC.

Acute Chest Syndrome in Children with Sickle Cell Disease in Italy: Results of a National Survey from the Italian Association of Pediatric Hematology Oncology (AIEOP)

Background: Acute Chest Syndrome (ACS) is the second cause of hospitalization in Sickle Cell Disease (SCD), burdened by significant morbidity and mortality. The guidelines regarding management of ACS are sometimes difficult to follow in the real world and the prevention and treatment strategies of ACS are often applied in an uneven manner in the various settings (community care, regional hospitals, reference university centers). Moreover, epidemiology, clinical phenotype and outcomes as well as risk factors could vary in different populations according to ethnicity, genotype or health care system organization. Aims and Methods: A retrospective multicenter observational study was conducted to investigate the epidemiology of ACS and to the evaluate the diagnostic and therapeutic pathways of ACS in children with SCD (age 0-18 years) in the 2013-2018 period, after the publication of the Italian Association of Pediatric Hematology Oncology (AIEOP) Guidelines for the Management of SCD in Childhood in Italy in 2012. Results: 126 children were recruited and 122 included in the analysis, with 208 evaluable episodes of ACS (range: 1-6 episodes /patient) from 11 AIEOP Centers. 73 M, 49 F. Mean age was 10.9 years. 85% patients were of African origin, 92% were HbSS/SB°; mean age at diagnosis of SCD of the entire cohort was 25,3 months (range 0-16,8). 44.2% of patients had more than one episode of ACS during the study period; 37% had had a previous episode before 2013. 58% had comorbidities, mostly respiratory (asthma or allergy). 75% of the patients underwent disease modifying treatment during study period (73% hydroxyurea, 2% chronic transfusion). The seasonality of ACS episodes was important in our country: 75% of episodes occured between October and March. 95% of ACS episodes were secondary to a Vaso-Occlusive Crisis. 76% of the admissions occurred in SCD reference centers, 24% in regional hospitals, but 30% later required transfer to reference centers for worsening of clinical conditions or need of exchange transfusion. The mean length of hospitalization was 9.6 days (range 1-46); one patient died of pneumococcal sepsis; 6 episodes required transfer to the Intensive Care Unit, mechanical ventilation was required in one episode. A good adherence to the AIEOP Guidelines was documented for some aspects: 99% of the patients were hospitalized, 98% performed chest X-ray for the diagnosis of ACS and in 99% antibiotic therapy was started. Others aspects were less satisfactory and in need of improvement: incentive spirometry was only performed in 19% of admissions; oxygen therapy was performed only in 75% of patients even if SatO2 was&lt;95%; transfer to reference centers was not always timely. During 75% of ACS episodes a simple red cell transfusion was required for Hb&gt;8g/dl, while in 16% an exchange transfusion was performed for severe respiratory distress (of these 71% were performed in patients transfered from regional hospitals); 38% required inhaled bronchodilators, 6% steroids. A preliminay evaluation of risk factors for recurrent ACS showed that in our cohort allergy to inhaled allergens (p 0.02) and enuresis (p 0.01) were associated with increased prevalence of recurrent ACS; patients with asthma/wheezing also presented more recurrent ACS compared to patients wihout them (23% vs 13%) but this data did not reach statistical significance. Conclusion: This study represents the first analysis in Italy of ACS, which is confirmed as a frequent event in our cohort, with a significant proportion of patients who experience recurrent ACS. Steps need to be undertaken to improve management of ACS and adherence to the AIEOP guidelines at a national level: stimulate the application of early preventive measures that are still under-utilized, increase the appropriateness of multidisciplinary specialist approach (transfusion specialist, acute care physicians, pneumologists, hematologists) strengthen the dissemination of information through training events for all the Hospitals of the network. Disclosures Colombatti: AddMedica: Consultancy; Global Blood Therapeutics: Consultancy; Novartis: Consultancy.

Crizanlizumab Treatment Is Associated with Clinically Significant Reductions in Hospitalization in Patients with Sickle Cell Disease: Results from the Sustain Study

Background: Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin (HbS), chronic hemolysis, recurrent pain episodes called vaso-occlusive crises (VOCs), multiorgan dysfunction and early death. VOCs decrease quality of life, are the main cause of healthcare encounters in SCD, and increase the risk of death. New therapies that reduce SCD hospitalizations are desirable given the potential to impact healthcare utilization, but also to reduce disease burden and decrease mortality and morbidity. The SUSTAIN study (Ataga et al. NEJM 2017), was a Phase 2, multicenter, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of crizanlizumab (2.5 and 5 mg/kg) with or without hydroxyurea therapy, in patients with SCD and a history of 2-10 VOCs in the previous 12 months (NCT01895361). The primary efficacy endpoint was annual rate of SCD-related pain crises (VOCs) leading to healthcare visit. The key secondary endpoint was annual rate of days hospitalized, regardless of cause. There was a statistically significant 45.3% reduction in median annual rate of VOCs leading to healthcare visit with crizanlizumab 5 mg/kg compared with placebo (1.63 vs 2.98 VOCs/year, P=0.01). There was a 41.8% reduction in median rate of days hospitalized with crizanlizumab 5 mg/kg compared with placebo (4.00 vs 6.87 days/year). Although this difference was not statistically significant (P=0.45), it appears to be clinically relevant. Methods: A post-hoc analysis of the SUSTAIN data was performed to better characterize the difference in the annual rate of days hospitalized between the crizanlizumab 5 mg/kg and placebo arms, and to compare the distribution of hospitalizations and time to first hospitalization. Results: As illustrated in Figure 1, a greater proportion of patients in the crizanlizumab arm (46%) were not hospitalized during the trial period (up to end of treatment) than in the placebo arm (35%). Correspondingly, the percentage of patients with ≥1 hospitalization was lower in the crizanlizumab (54%) than the placebo arm (65%). In addition, a trend for delayed time to first hospitalization shown in Figure 1 was further explored with a Kaplan-Meier (KM) analysis (Figure 2). Figure 2 shows clear separation of the curves, evident from Month 1 of treatment. The median time to first hospitalization was greater with crizanlizumab 5 mg/kg than with placebo (6.3 vs 3.2 months; hazard ratio [HR] 0.683 [95% CI 0.437-1.066]). The apparent improvement in time to first hospitalization is consistent with previously published SUSTAIN results regarding median time to first VOC leading to healthcare visit. Patients treated with crizanlizumab 5 mg/kg were found to experience a longer median time to first VOC leading to healthcare visit than patients on placebo (4.07 vs 1.38 months; HR 0.50 [95% CI 0.33-0.74]). Conclusions: The primary SUSTAIN results showed that crizanlizumab reduced VOCs leading to a healthcare visit. This analysis demonstrates additional positive trends associated with crizanlizumab treatment compared to placebo, regarding the percentage of patients with no hospitalizations and a delayed time to first hospitalization. Together, these findings provide further evidence that crizanlizumab may have a beneficial impact on reducing hospitalizations. Disclosures Ataga: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Modus Therapeutics: Honoraria. Kutlar:Micelle Biopharma: Other: DSMB Chair; Novartis: Consultancy; Global Blood Therapeutics, Inc. (GBT): Research Funding; Novo Nordisk: Research Funding; Bluebird Bio: Other: DSMB Member. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. Lincy:NOVARTIS PHARMA AG: Employment. Kanter:Novartis: Consultancy, Honoraria; Imara: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Guidepoint Global: Consultancy; GLG: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy.

Safety of Intravenous Arginine Therapy in Children with Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain: A Randomized Placebo-Controlled Trial in Progress

Safety of Intravenous Arginine Therapy in Children with Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain: A Randomized Placebo-Controlled Trial in Progress

Impact of Depression in Sickle Cell Disease Hospitalization-Related Outcomes: An Analysis of the National Inpatient Sample (NIS).

Background and objectives: This study aimed to analyze and discern the differences in demographics and inpatient outcomes (length of stay (LOS), total charges, disease severity, and mortality) between depressed versus non-depressed sickle cell disease (SCD) patients. Materials and Methods: A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010–2014). We identified 73,225 SCD hospitalizations and comorbid depression (6317, 8.6%) as the primary and the other diagnosis, respectively, using International Classification of Diseases (ICD)-9 codes. We used linear and logistic regression model to evaluate the changes in inpatient outcomes. Results: Comorbid depression was more prevalent among middle-aged adults (11.5%), females (10.63%), and whites (12.43%). We did not find any association between income and comorbid depression among SCD patients. After adjusting for the demographic covariates, comorbid depression remained a significant risk factor for longer LOS (mean difference −1.16 days, 95% CI −1.30 to −1.03) and higher total charges (mean difference −USD5058, 95% CI −6261 to −3855) during hospitalization. SCD with comorbid depression was also significantly associated with a higher number of chronic conditions (mean difference −2.08, 95% CI −2.13 to −2.03) and 1.5 times (95% CI 1.39 to 1.63) higher odds of major severity of illness. Conclusion: Comorbid depression was significantly associated with longer LOS, more severity of illness, and higher hospital charges. Healthcare providers caring for adults with SCD should consider screening for and treating comorbid depression to improve the health-related quality of life.

Reduction in Hospital Days Using a Multidisciplinary Approach for Pediatric Patients with Sickle Cell Disease

Background: Pain crisis is the most frequent reason for admission in children with sickle cell disease (SCD). Frequent hospitalizations are associated with school absenteeism, emotional distress, and financial hardships. There is limited literature on initiatives to decrease admissions and hospital days in SCD pain crises. Prior studies have shown that individualized pain plans in emergency rooms can decrease admission rates and that a multidisciplinary approach with provider and patient education and close follow up can decrease 30-day readmission rates. Our goal was to decrease hospital days for pain crisis admissions by 40% over a 5-year period using a multidisciplinary approach.Methods: From September 2011 to August 2016 a multidisciplinary quality improvement project was conducted. A Plan-Do-Study-Act methodology was used. Five key drivers were identified and nine interventions were implemented. Interventions for the entire cohort included individualized home pain plans, emergency room and inpatient order sets, inpatient daily schedules, and a psychoeducation and biofeedback program. High utilizers, defined as ≥ 4 admissions per year, had an individualized SCD plan and were assigned a mental health provider. The high utilizer group was expanded to include at risk patients (3 admissions per year). Data was analyzed for all patients age 0-21 years admitted for SCD pain crises. The primary measure was hospital days, with 30-day readmission rate as a balancing measure.Results: 216 SCD patients were followed in 2011, with a 14% increase over the five year study period. From this cohort, a total of 122 patients were admitted for pain crises during this time. 48% of admitted patients were male, with a mean age of 10.68±5.65 years, and 72% had hemoglobin SS disease (16% SC, 5% Sβ0, 7% Sβ+). As shown in Table 1, the number of patients admitted decreased from 55 patients (25.4% of total SCD patients) in the pre-intervention period to 33 patients (13.3% of total SCD patients) in the final year of the intervention (p = 0.0014). The number of admissions decreased from 148 admissions in the pre-intervention period to 86 admissions in the final year of the intervention (54.7% decrease). The number of hospital days decreased by 61% from 59.6 days per month in the pre-intervention period to 23.2 days per month in the final year of the intervention (p < 0.0001). Number of high utilizers decreased from 13 patients in the pre-intervention period to 7 patients in the final year of the intervention. There was a 66% reduction in the number of hospital days in the high utilizer group compared to a 47% reduction in the low utilizer group. The 30-day readmission rate decreased from 33.9% pre-intervention to 19.4% in the final year of intervention. Special cause variation was first achieved in April 2014, 18 months after the start of all interventions, with a shift of the centerline from 59.6 days/month to 38.3 days/month and again in February 2016 with a decrease to 23.2 days/month (Figure 1). There was special cause variation in 30-day readmissions in April 2014 with a centerline shift in the 30-day readmission rate from 33.9% to 19.4%. The baseline direct hospital cost for SCD admissions was $909,000 per year. In the final year of the project, the average cost was $353,880 per year, with an overall annual savings of $555,120 in direct hospital costs.Conclusion: In this single center study, the multidisciplinary approach of effective home, emergency room, and inpatient pain management combined with increased mental health services for higher risk individuals proved to be effective in decreasing SCD pain crisis admissions and hospital days. A dedicated team effort with simple interventions had a significant impact on the well-being of the entire SCD population, but especially those who were more frequent utilizers of the healthcare system, while decreasing hospital costs, and can serve as a model for other institutions. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

PND109 - SICKLE-CELL DISEASE RELATED HOSPITALIZATIONS IN FRANCE : A REGIONAL DESCRIPTIVE ANALYSIS FROM THE FRENCH MEDICAL INFORMATION SYSTEM DATABASE IN 2016

The objective of this study was to assess the number of patients hospitalized for sickle-cell disease (SCD) in France and for each region, and to estimate the proportion of patients experiencing Vaso-Occlusive Crisis (VOC) and Blood Transfusions (BT). A cross sectional study of all 2016 hospital stays related to SCD, using ICD10 codes as D57.(0/1/2 or 8) as PD/RD (principal/related diagnosis) or SAD (significantly associated diagnosis), were extracted from the French national hospital discharge database (PMSI). Thanks to their unique ID, patients have been tracked over hospital stays. VOC has been defined by the ICD10 code D57.0 as PD/RD, and BT has been defined by the ICD 10 code Z513 and/or the French CCAM codes (FELF00(4/5/7/11/12 or FEPF003)). Annual rates of hospitalized patient were standardized on age and sex using population residing in France on 1 January 2015 as reference. In 2016, 38,550 SCD stays for 13,059 patients (2.95 hospitalizations by patient in average) were included. Among these patients, 5.6% received only BT, 38.4% developed a VOC, and 10.8% had both. The situation was more complex at a regional level with 52.2 % of patients hospitalized in “Ile de France” region, compared to the others which oscillated between 1.0 % to 5.1%. The French 5 overseas departments collectively managed 15.9 % of these patients. The standardized rate of hospitalizations is higher in overseas departments compared to the other regions in France, respectively 97.80 vs 16.98 per 100,000 inhabitants. The same difference is showed in metropolitan France, with a higher standardized rate in “Ile de France” compared to the other regions, respectively 51.95 vs 4.20 to 14.55 per 100,000 inhabitants. This descriptive study showed real differences in SCD hospital management according to regions which could help health public policy to better manage this disease.

Acute Vaso-Occlusive Pain Associated with the Onset of Menstruation Is Distinct from Dysmenorrhea in Sickle Cell Disease

*Deva Sharma, MD, MS, and Melissa Day, BS, contributed equally to the abstract and are co-first authorsIntroduction:Acute vaso-occlusive pain episodes are the primary reason for hospitalization in sickle cell disease (SCD) and predict mortality in adults. Women with SCD have higher pain rates than men, particularly during their reproductive years. Studies of the temporal relationship between the onset of menstruation and acute vaso-occlusive pain have reached conflicting conclusions. Healthcare providers often do not recognize the temporal relationship between the onset of menstruation and acute vaso-occlusive pain, with the common perception that acute vaso-occlusive pain is synonymous with dysmenorrhea. In sequentially independent cross-sectional studies involving discovery and confirmatory cohorts, we tested the hypothesis that acute vaso-occlusive pain is associated with the onset of menstruation in women with SCD and is distinct from dysmenorrhea. Evidence to support our hypothesis was based on identifying four distinct groups: 1) women with dysmenorrhea without acute vaso-occlusive pain associated with menstruation, 2) women with acute vaso-occlusive pain associated with menstruation without dysmenorrhea, 3) women with both, and 4) women with neither.Methods:Discovery cohort : In an initial cross-sectional study, we interviewed women in the outpatient and inpatient settings at Vanderbilt University and Wayne State University (Figure 1). After obtaining informed consent, we conducted self-administered surveys which included a validated questionnaire to define acute vaso-occlusive pain associated with menstruation and dysmenorrhea (Behav Res Ther 1975, 13(4):237-44). Acute vaso-occlusive pain associated with menstruation and dysmenorrhea were defined by temporal and frequency criteria so that participants could meet either or both criteria (Table 1). Associations of clinical and demographic variables with acute vaso-occlusive pain triggered by menstruation and dysmenorrhea were evaluated by the chi-square test and t-test, and then in a multivariable regression model. The proportions of women who met criteria for acute vaso-occlusive pain associated with menstruation and dysmenorrhea were determined. A p-value of 0.05 was considered significant for all analyses.Confirmatory cohort : In a subsequent cross-sectional study, we conducted an identical online questionnaire using select websites (Figure 1) to validate our initial findings. Statistical analyses were identical to the discovery cohort.Results:Discovery cohort : A total of 95 women were surveyed using face-to-face questionnaires. Baseline characteristics are summarized in Table 2. Twenty-eight women (29.5%) met defined criteria for acute vaso-occlusive pain associated with menstruation. Age (p=0.211) and genotype (p=0.343) were not associated with acute vaso-occlusive pain triggered by menstruation. Sixty-two women (65.3%) met criteria for dysmenorrhea. Importantly, among the 95 participants in the discovery cohort, 3% met criteria for acute vaso-occlusive pain associated with menstruation alone, in the absence of dysmenorrhea, while 26% met criteria for both acute vaso-occlusive pain associated with menstruation and dysmenorrhea (Figure 2).Confirmatory cohort : A total of 118 women were surveyed using the online questionnaires. Baseline characteristics were comparable between the discovery and confirmatory cohorts. Forty-three women (36.4%) met defined criteria for acute vaso-occlusive pain associated with menstruation. Sixty-six women (55.9%) met criteria for dysmenorrhea. Importantly, among the 118 participants in the confirmatory cohort, 14% met criteria for acute vaso-occlusive pain associated with menstruation alone, in the absence of dysmenorrhea, while 22% met criteria for both acute vaso-occlusive pain associated with menstruation and dysmenorrhea (Figure 2).Conclusions:The onset of menstruation in women with SCD is another, yet unrecognized risk factor for acute vaso-occlusive pain episodes. Further studies are needed to better define the underlying mechanism and facilitate the development of targeted therapies for affected women. [Display omitted] DisclosuresRodeghier:Rodeghier consultants: Consultancy. Callaghan:Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Site PI, Research Funding; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Site PI, Speakers Bureau; Roche; Shire: Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Grifols: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Speakers Bureau; Alnylam Pharmaceuticals, Inc: Other: Owns stock, stock options, or bonds ; Global Blood Therapeutics: Other: Site PI; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees; Sancillio: Other: Site PI; Bayer HealthCare; Pfizer Inc.; Roche; Shire: Consultancy; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Association of Guideline-Adherent Antibiotic Treatment With Readmission of Children With Sickle Cell Disease Hospitalized With Acute Chest Syndrome

Acute chest syndrome (ACS) is a common, serious complication of sickle cell disease (SCD) and a leading cause of hospitalization and death in both children and adults with SCD. Little is known about the effectiveness of guideline-recommended antibiotic regimens for the care of children hospitalized with ACS. To use a large, national database to describe patterns of antibiotic use for children with SCD hospitalized for ACS and to determine whether receipt of guideline-adherent antibiotics was associated with lower readmission rates. Retrospective cohort study including 14 480 hospitalizations in 7178 children (age 0-22 years) with a discharge diagnosis of SCD and either ACS or pneumonia. Information was obtained from 41 children's hospitals submitting data to the Pediatric Health Information System from January 1, 2010, to December 31, 2016. National Heart, Lung, and Blood Institute guideline-adherent (macrolide with parenteral cephalosporin) vs non-guideline-adherent antibiotic regimens. Acute chest syndrome-related and all-cause 7- and 30-day readmissions. Of the 14 480 hospitalizations, 6562 (45.3%) were in girls; median (interquartile range) age was 9 (4-14) years. Guideline-adherent antibiotics were provided in 10 654 of 14 480 hospitalizations for ACS (73.6%). Hospitalizations were most likely to include guideline-adherent antibiotics for children aged 5 to 9 years (3230 of 4047 [79.8%]) and declined to the lowest level for children 19 to 22 years (697 of 1088 [64.1%]). Between-hospital variation in antibiotic regimens was wide, with use of guideline-adherent antibiotics ranging from 24% to 90%. Children treated with guideline-adherent antibiotics had lower 30-day ACS-related (odds ratio [OR], 0.71; 95% CI, 0.50-1.00) and all-cause (OR, 0.50; 95% CI, 0.39-0.64) readmission rates vs children who received other regimens (cephalosporin and macrolide vs neither drug class). Current approaches to antibiotic treatment in children with ACS vary widely, but guideline-adherent therapy appears to result in fewer readmissions compared with non-guideline-adherent therapy. Efforts to increase the dissemination and implementation of SCD treatment guidelines are warranted as is comparative effectiveness research to strengthen the underlying evidence base.

IMPROVING OUTPATIENT FOLLOW-UP AFTER DISCHARGE FROM HOSPITAL FOR PATIENTS WITH SICKLE CELL DISEASE AT HIGH RISK FOR READMISSION

Abstract BACKGROUND: Recent evidence has shown that outpatient follow-up after hospitalization plays an important role in reducing readmission rates for patients with Sickle Cell Disease (SCD). Reducing 28-day readmission rates in patients with SCD has become an established part of our hospitals quality improvement (QI) plan. OBJECTIVES: To increase the proportion of SCD patients at high risk for readmission who receive outpatient Hematology follow-up within 14 days of discharge from 28% to 90%. DESIGN/METHODS: SCD patients at high risk for readmission were defined (based on literature) as those with 3 hospital admissions for vaso-occlusive episodes (VOE) or 1 admission for acute chest syndrome (ACS) within 12 months of the index admission. An interdisciplinary team created a process map to identify barriers and opportunities for improvement. In July 2015, multimodal process steps were introduced using posters, emails, and presentations to direct medical trainees, registered nurses and ward clerks to identify high risk patients, inform the SCD team of admissions, ensure follow-up is booked within 14 days, and confirm with families prior to discharge. A pre- and post-intervention chart review (quarterly, July 2014 through December 2015) was performed on all SCD hospital admissions identified as crisis by ICD10 code 57.0, which includes VOE, ACS and splenic sequestration. RESULTS: During the 18-month period, there were 223 hospital admissions for 131 patients. Forty-seven percent of admissions were for high-risk patients. Fifty-five percent of patients were taking hydroxyurea at the time of index admission. The 28-day readmission rate was 12.6%, and did not change significantly over the time period. There was no difference in readmission rates between high-risk and standard-risk patients. The mean number of days from discharge to follow-up for patients prior to initiation of the intervention (July 2015) was 40 days, and only 28% of high-risk patients were seen in Hematology clinic within 14 days of discharge. In the first quarter after the introduction of the process steps, this improved to 16 days and 73%, respectively. The improvement, however, was not sustained into the final quarter. CONCLUSION: Our multimodal strategy resulted in improved time to follow-up for SCD patients at high risk for readmission. The lack of maintenance into the final quarter suggests the need for ongoing education to sustain positive changes. Further data collection is required to determine the impact of improved time to follow-up on readmission rates.

Use of gabapentin in the treatment of chronic pain in an adolescent with sickle cell disease

Vaso-occlusive crises are the most common manifestation of sickle cell disease (SCD) and the main cause of hospital admission in these patients. There is emerging evidence that vaso-occlusive pain has...

Nucleated Red Blood Cells in Children with Sickle Cell Disease Hospitalized for Acute Vaso-Occlusive Pain

Background: Acute vaso-occlusive crises (VOC) represent the most common reason for hospitalization among children with sickle cell disease (SCD). Acute chest syndrome (ACS) and severe hemolysis, both of which may require transfusion, are common complications during hospitalizations for VOC. Despite the high morbidity associated with these complications, there are currently no reliable clinical predictors of ACS and transfusion requirement in this setting. Nucleated red blood cells (NRBC), reported as the number of NRBC/100 white blood cells (WBC) on a complete blood count (CBC), may reflect marrow necrosis or increased erythropoetic drive, yet their relationship to VOC and its complications have not been studied. We aimed to evaluate the relationship between admission NRBC and development of ACS or transfusion requirement in children with SCD hospitalized for VOC. We hypothesized that higher admission NRBC is associated with greater risk of ACS/transfusion in this population. Methods: We performed a single-institution, retrospective review of all hospitalizations from 2011 through 2015 for uncomplicated VOC in children with SCD. Hospitalization encounters were identified by ICD-9 codes for SCD and use of parenteral opioids for at least 24 hours in the electronic medical record. Data extracted from encounters meeting inclusion/exclusion criteria included all CBCs and clinical outcomes. Between-group comparisons were performed by Mann-Whitney U test and Pearson's chi-square test for continuous and categorical variables, respectively, as well as by Spearman's rank order correlation (SPSS V24). The relationship of admission and change in NRBC (∆NRBC) to complications was evaluated by binary logistic regression and adjusted for significant co-variates on bivariate analysis. For ∆NRBC, we used the final CBC obtained prior to a complication or prior to discharge for encounters not resulting in a complication. Results: We reviewed 271 encounters for uncomplicated VOC in 96 patients (mean age 13.1 years, 47% male, and 76% Hb SS or S/β0 thalassemia). Overall, 48/271 (18%) encounters for VOC resulted in ACS/transfusion, or both. Median NRBC on admission was 2 /100 WBC (range 0 to 137 /100 WBC) for all encounters. Admission NRBC was significantly correlated with age (r = 0.15, p = 0.02), % reticulocytes (r = 0.18, p &lt; 0.01) and hemoglobin (r = 0.39, p &lt; 0.001). Median admission NRBC was higher among patients on hydroxyurea (3 vs. 1.8 /100 WBC, p &lt; 0.01) but did not differ by sex or genotype. In general, median admission NRBC did not differ between hospitalizations that did or did not result in ACS/transfusion (2 vs 2.5 /100 WBC, p = 0.91). In our logistic regression model that included NRBC, % reticulocytes, WBC, hemoglobin, platelets and genotype as co-variates, only lower hemoglobin (p = 0.02) and higher WBC (p &lt; 0.001) on admission were independently associated with ACS/transfusion. A second CBC was obtained in 110/271 (41%) encounters reviewed. Median ∆NRBC was 0 /100 WBC (range -37 to 116 /100 WBC) in these encounters. ∆NRBC was significantly correlated with age (r = 0.2, p = 0.04) but not with change in other lab values. Median ∆NRBC was higher among patients with a history of hypertension (0 vs. 13 /100 WBC, p &lt; 0.01) but did not differ by hydroxyurea status, sex or genotype. Importantly, we found that median ∆NRBC was significantly higher in hospitalizations that resulted in ACS/transfusion compared to those that did not (0 vs 2 /100 WBC, p &lt; 0.01). By logistic regression, greater ∆NRBC (p &lt; 0.01) and lesser ∆platelets (p = 0.04) were independently associated with higher risk of ACS/transfusion after adjustment for ∆hemoglobin and genotype. A receiver operating characteristic curve constructed from a logistic regression model that included only ∆NRBC, admission WBC, admission hemoglobin and ∆platelets resulted in an area under the curve of 0.82. Conclusions: We found no relationship between admission NRBC and complications during hospitalization for VOC in children with SCD. Greater ∆NRBC, however, was independently associated with development of ACS/transfusion requirement during hospitalization for VOC, suggesting ∆NRBC may represent a useful biomarker for predicting complications in children with SCD hospitalized for VOC. Clinical decision rules that incorporate the careful monitoring of ∆NRBC in this setting should be prospectively studied. Disclosures No relevant conflicts of interest to declare.

Widespread Pain Among Youth With Sickle Cell Disease Hospitalized With Vasoocclusive Pain: A Different Clinical Phenotype?

The purpose of this study was to describe the clinical phenotype of widespread pain (WSP) among youth with sickle cell disease (SCD) hospitalized with vasoocclusive pain. One hundred fifty-six youth with SCD, between 7 and 21 years of age hospitalized at 4 children's hospitals for a vasoocclusive episode were evaluated. Data were collected during 1 day of the hospitalization. Using the 2010 American College of Rheumatology guidelines, 21.8% of patients were identified as having WSP (pain in 7 or more unique body locations). Patients classified as having WSP had higher pain intensity (6.5 vs. 5.6; t=2.19, P=0.03) higher pain burden (13.0 vs. 9.8; t=3.09, P=0.002), higher acute functional disability (22.1 vs. 16.5; t=2.43, P=0.016), higher chronic functional disability (30.4 vs. 22.2; t=2.31, P=0.02), lower positive affect (22.9 vs. 27.6; t=2.23, P=0.027), and lower quality of life (56.2 vs. 62.9; t=1.99, P=0.049) than those youth with SCD without WSP. Assessment of WSP may identify a unique clinical phenotype of youth with SCD with differing treatment needs.

Guideline on the management of acute chest syndrome in sickle cell disease.

1. Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust 2. Lane Fox Respiratory Unit, St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust 3. Department of Haematology, North Middlesex Hospital 4. Department of Paediatric Haematology, Bristol Royal Hospital for Children 5. Department of Haematological Medicine, King’s College Hospital 6. Department of Haematology, Whittington Hospital

Role of Self-Care in Sickle Cell Disease

Self-care is an important aspect of managing a chronic disease. In sickle cell disease (SCD), home self-care contributes to individual pain management and thus pain crisis prevention. A better understanding of self-care can help health care providers equip patients with the resources and skills necessary to participate in their disease management. The aim of this study was to examine factors that influence self-care among young adults with SCD. A descriptive, cross-sectional study was conducted using secondary data analysis. Participants were recruited from two SCD clinics in the southeastern United States. The sample consisted of 103 young adults, ages 18 to 30 years, with SCD. Bivariate correlations and regression analyses were used to evaluate the relationships among SCD self-efficacy, social support, sociodemographics, self-care, and hospital visits for pain crises. Study participants were primarily women (61.2%), unemployed or disabled (68%), lived with family (73.8%), and had an annual average of three hospital visits for pain crises. Participants, on average, had 12 years of education, an annual household income of $35,724, and were 24 years old. Social support (p = .001), SCD self-efficacy (p = .002), and years of education (p = .043) were significantly related to self-care. Of the hypothesized variables, only income was significantly associated with hospital visits for pain crises (r = −0.219, p = .05). Individuals with SCD may benefit from self-care interventions that enhance social support, SCD self-efficacy, and access to education. To inform intervention development, further investigation is needed regarding daily self-care behaviors used by young adults with SCD.

Trends In the Hospital Treatment of Sickle Cell Disease-Related Priapism In the United States: 1998 to 2007,

Abstract 4195 OBJECTIVE:Priapism is a serious complication of sickle cell disease (SCD). Urologic guidelines recommend that the management of priapism should entail intracavernous treatment in addition to treatment for the underlying condition. One meta-analysis suggests that transfusion is an ineffective and potentially harmful therapy for priapism in SCD. Nevertheless, little is known about how priapism is actually managed for these patients. We examined in-hospital treatment trends of priapism among male SCD patients in the United States (US) over a 10-year period with a focus on the use of blood transfusion. METHODS:This is a retrospective analysis of the Nationwide Inpatient Sample (1998 – 2007). Priapism patients were identified based on ICD-9 code 607.3. The analysis was restricted to male patients with an ICD-9 code for SCD. We assessed the total number of priapism discharges over time and by year. We also assessed the overall and annual prevalence of blood transfusions, exchange blood transfusions (EBTs), and penile surgeries for all discharges under study. We postulated that transfusions given in patients not undergoing surgery were likely given as primary treatment in the management of priapism. RESULTS:An estimated 502,577 qualifying male SCD hospitalizations were identified. Among these, 9,861 (2%) were priapism-related. The mean age of the male SCD hospitalizations was 24.9, with only a 1 year difference found between non-priapism and priapism discharges. The proportion of priapism related hospitalizations remained stable over time, ranging from 1.7% to 2.4% (p = 0.359). Overall, priapism related discharges were more likely than non-priapism related discharges to be treated with blood transfusions (36.3% vs. 22.6%, p < 0.0001), EBTs (7.6% vs. 1.0%, p < 0.0001), and penile surgeries (14.3% vs. < 0.1%, p < 0.0001). There was no association between the prevalence of penile surgery and blood transfusions among priapism discharges over the entire time period, and there was no evidence that the association between penile surgeries and blood transfusions for priapism patients changed over time. Approximately 14% of priapism discharges with no blood transfusion underwent penile surgery compared to 15.2% of priapism discharges with a blood transfusion (p = 0.411). Linear trend analyses revealed a 9% increase each year in the use of blood transfusions as a treatment for all male SCD hospitalizations, regardless of priapism status (OR = 1.09, p < 0.001). Adjusting for the temporal trend, priapism related discharges were nearly twice as likely as non-priapism related discharges to be treated with blood transfusions of any type (OR = 1.99, p < 0.001). There was, however, a significant association between the prevalence of penile surgery and exchange blood transfusions among priapism patients as 27.1% of priapism discharges with an exchange transfusion underwent penile surgery compared to 13.2% of discharges without an exchange transfusion (p < 0.0001). There was no evidence of a significant linear trend in the use of EBT in the treatment of any male SCD hospitalization over time (OR = 1.01, p = 0.691). Overall, priapism related discharges were 8-times more likely than non-priapism related discharges to be treated with EBT (OR = 8.1, p < 0.001). There was no significant linear temporal trend in the use of penile surgeries in the treatment of priapism related discharges (OR = 1.04, p = 0.209). Priapism discharges in which a penile surgery occurred were more than twice as likely to receive an exchange blood transfusion than those priapism discharges without a penile surgery (OR = 2.42, p < 0.001). CONCLUSIONS:The use of EBT and penile surgeries in the treatment of priapism related SCD discharges appears to be relatively stable over time, while there has been an increase in the use of blood transfusions of any kind for all male SCD hospitalizations, including those with priapism. The lack of an association between the prevalence of blood transfusions of any type and the use of penile surgery among priapism patients suggests that blood transfusions continue to be used as a primary treatment modality for priapism, even though data to support the effectiveness of transfusion is lacking. Patient and hospital-level factors that may impact the use of different treatment options for priapism need to be assessed, and the outcomes of the variations in the treatment of priapism related SCD hospitalizations should be examined. Disclosures:No relevant conflicts of interest to declare.