Episodes Of Acute Chest Syndrome Research Articles

Allergic Sensitization Is Associated with Decreased Risk of ED Visits and Hospitalizations for Pain in Sickle Cell Disease

Rationale: Lower airway disease is common in pediatric sickle cell disease (SCD) and is often diagnosed as asthma. This condition may be a risk factor for acute chest syndrome (ACS) and pain episodes. There are conflicting data about whether SCD-associated lower airway disease is due to allergic inflammation, as is typical in non-SCD childhood asthma. However, transgenic SCD mouse models have suggested a propensity toward allergic inflammation, and a recent study in children with SCD suggested allergic sensitization was associated with increased risk of acute chest syndrome (ACS). Allergic sensitization may be a risk factor for pulmonary inflammation and may trigger pain episodes. We hypothesized that allergic sensitization to a panel of indoor allergens would be associated with more frequent ED visits and hospitalizations for pain, ACS, and asthma symptoms in children and adolescents with SCD.Methods: Patients were recruited from two large academic children's hospitals. Ninety-nine participants with SCD ages 5-21 who were not receiving chronic exchange transfusions completed pre- and post-bronchodilator spirometry and allergy testing at a baseline visit. Allergen-specific IgE in blood was measured to Alternaria, Aspergillus, cat, cockroach, dog, dust mite (D. farinae), and mouse urine protein; we examined baseline characteristics by stratified groups (not sensitized vs. sensitized to one or more allergens) via t-tests, chi square, and Mann-Whitney U tests; we created a count variable with number of sensitizations. ED visits and hospitalizations were reviewed retrospectively two years prior to study entry. Asthma was defined as physician diagnosis in medical records plus at least one home asthma medication (albuterol or controller/preventative medication). We used negative binomial models to examine relationships between atopy [number of positive specific IgE (³0.35kU/L)] and the number of ED visits and hospitalizations, adjusting for age, sex, hydroxyurea use, and head of household (HOH) education level. FEV1 and positive bronchodilator response (³10%) were compared via multiple linear regression and multiple logistic regression.Results: Participants were 41% male, 66% HbSS or HbSb0 genotype, 52% on hydroxyurea, and 32% had a HOH with a high school education or less [Table]. Twenty-eight percent had a physician diagnosis of asthma, and 57% (N=56) were sensitized to at least one allergen. Allergic sensitization was associated with decreased risk of total ED visits1 (IRR 0.80[0.66-0.97] p=0.022), ED visits for pain (IRR 0.80[0.67-0.97] p=0.019), and fever (IRR 0.63[0.45-0.88] p=0.007), but not associated with a significant difference in ED visits for asthma or ACS. Allergic sensitization was neither associated with differences in rates of hospitalization (total, or for pain, fever, ACS, or asthma) nor with differences in FEV1 percent predicted, FEV1/FVC ratio, or positive bronchodilator response.Conclusions: In a population of children with SCD, allergic sensitization was associated with decreased risk of ED visits (total, for pain, and for fever). The mechanism for an association between atopy and a less severe phenotype of SCD is unclear. These findings point to potential differences in immunologic endotype/phenotype and add support to the hypothesis that lower airway disease in children with SCD has a different mechanism than typical childhood atopic asthma. Further investigation into the immunologic phenotypes and mechanisms of lower airway disease in children with SCD is warranted.1All IRR presented are per allergen, adjusted for age, sex, hydroxyurea use, and HOH education level; 95% confidence interval. [Display omitted] DisclosuresStrouse:Global Blood Therapeutics: Consultancy.

Factors Associated With Mechanical Ventilation Use in Children With Sickle Cell Disease and Acute Chest Syndrome.

Acute chest syndrome is the leading cause of death in children with sickle cell disease and is generally due to respiratory failure. Epidemiologic factors for a need for mechanical ventilation in children with acute chest syndrome require further clarification. Retrospective observational study. Nationally representative pediatric inpatient records in the United States by using the Kids' Inpatient Database for the years 2003, 2006, 2009, and 2012. Patients age less than 20 years old with a discharge diagnosis of acute chest syndrome. Data were weighted to estimate annual hospitalizations according to hospital characteristics in the United States. Multivariable logistic regression was conducted to ascertain factors associated with use of mechanical ventilation, after adjusting for patient and hospital characteristics. Total hospitalizations for acute chest syndrome were 5,018 in 2003, 6,058 in 2006, 6,072 in 2009, and 6,360 in 2012. Mechanical ventilation use was associated with comorbidities of obesity (odds ratio, 3.35; 95% CI, 1.94-5.78), obstructive sleep apnea (odds ratio, 3.72; 95% CI, 2.23-6.20), and heart disease (odds ratio, 2.19; 95% CI, 1.47-3.27). In addition, nonblack compared with black children (odds ratio, 1.53; 95% CI, 1.02-2.31) and the fall season (p = 0.018) were associated with mechanical ventilation use. Comorbidity of obesity, obstructive sleep apnea, or heart disease could be potentially associated with mechanical ventilation use during an episode of acute chest syndrome. Prospective observational studies would be required to confirm these findings and infer potential interventions for preventing illness severity.

Early Noninvasive Ventilation and Nonroutine Transfusion for Acute Chest Syndrome in Sickle Cell Disease in Children: A Descriptive Study.

To describe the need for transfusion and short- and long-term evolutions of pediatric sickle cell disease patients with acute chest syndrome for whom early continuous noninvasive ventilation represented first-line treatment. Single-center retrospective chart study in PICU. A tertiary and quaternary referral PICU. All sickle cell disease patients 5-20 years old admitted with confirmed acute chest syndrome and not transfused in the previous month were included. None. Demographic data, laboratory and radiologic findings, transfusions, invasive ventilation, oxygen and noninvasive ventilation settings, duration of opioid treatment, length of hospital stay, and severe sickle cell disease complications in the ensuing 2 years were extracted from medical charts. Sixty-six acute chest syndrome in 48 patients were included. Continuous early noninvasive ventilation was well tolerated in 65 episodes, with positive expiratory pressure 4 cm H2O and pressure support 10 cm H2O (median) administered continuously, then discontinued during 7 days (median). No patient necessitated invasive ventilation or died. Twenty-three acute chest syndrome (35%) received transfusions; none received blood exchange. Transfused patients had more frequent upper lobe radiologic involvement, more severe anemia, higher reticulocyte counts, and higher C-reactive protein than nontransfused patients. Their evolution was more severe in terms of length of opioid requirement, length of noninvasive ventilation treatment, overall time on noninvasive ventilation, and length of stay. At 2-year follow-up after the acute chest syndrome episode, no difference was observed between the two groups. Early noninvasive ventilation combined with nonroutine transfusion is well tolerated in acute chest syndrome in children and may spare transfusion in some patients. Early recognition of patients still requiring transfusion is essential and warrants further studies.

Age is a predictor of a small decrease in lung function in children with sickle cell anemia.

The longitudinal pattern of lung function in children with sickle cell anemia (SCA) has shown a decrease in FEV1 % predicted, a risk factor for death in adults with SCA, but predictors for this decline are poorly characterized. In a prospective longitudinal multi-center cohort of children with SCA, we tested the hypotheses that: (1) FEV1 % predicted declines over time; and (2) SCA-specific characteristics and therapy predict this decline. At three clinical centers, children with SCA (HbSS or HbSβ0 thalassemia), unselected for respiratory disease, were enrolled in the Sleep and Asthma Cohort (SAC) study. Study-certified pulmonary function technicians performed spirometry and lung volumes. Each assessment was reviewed centrally. Predicted values were determined for TLC, FEV1 , FVC, and FEV1 /FVC ratio. A total of 197 participants, mean age 11.0 years at first testing (range 4-19.3 years), had a minimum of three spirometry measurements, over an average of 4.4 years (range 1.1-6.5 years) from baseline to endpoint. In a multivariable model, FEV1 % predicted declines by 0.3% for every additional year of age (95% CI -0.56 to -0.05, P = .020). Sex, asthma history, hemoglobin, reticulocyte count, white blood cell count, incidence rate of severe acute pain and acute chest syndrome episodes, and hydroxyurea therapy were not associated with a decline in FEV1 % predicted. In a large, rigorously evaluated, prospective cohort of an unselected group of children with SCA, FEV1 % predicted declines minimally over an average of 4 years, and none of the examined disease features predict the decline.

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P<0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P=0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA.

Associations between endothelial dysfunction and clinical and laboratory parameters in children and adolescents with sickle cell anemia.

BackgroundHematological changes can drive damage of endothelial cells, which potentially lead to an early endothelial dysfunction in patients with sickle cell anemia (SCA). An association may exist between endothelial dysfunction and several clinical manifestations of SCA. The present study aims to evaluate the links between changes in endothelial function and clinical and laboratory parameters in children and adolescents with SCA.MethodsThis study included 40 children and adolescents with stable SCA as well as 25 healthy children; aged 6–18 years. All study subjects were evaluated for endothelial function using Doppler ultrasonography. In addition, a number of laboratory assays were performed, including reticulocyte and leukocyte counts as well as measurement of circulating levels of total bilirubin, C-reactive protein (CRP), glucose, lipoproteins and peripheral oxyhemoglobin saturation. These parameters were also compared between SCA patients who were undertaking hydroxyurea (HU) and those who were not.ResultsFlow-mediated vasodilation (FMD) values were found to be reduced in SCA patients compared with those detected in healthy controls. SCA individuals with lower FMD values exhibited higher number of hospital admissions due to vaso-occlusive events. Additional analyses revealed that patients who had decreased FMD values exhibited higher odds of acute chest syndrome (ACS) episodes. A preliminary analysis with limited number of individuals failed to demonstrate significant differences in FMD values between SCA individuals who were treated with HU and those who were not.ConclusionsChildren and adolescents with SCA exhibit impaired endothelial function. Reductions in FMD values are associated with ACS. These findings underline the potential use of FMD as screening strategy of SCA patients with severe prognosis at early stages.

Clinical and Hematological Evaluation of Patients with Sickle Cell Anemia Before and After Four Years of Using Hydroxyurea

Objective: Evaluating clinical and hematological-clinical parameters of patients with sickle cell anemia (SCA) before and after four years of using hydroxyurea (HU). &#x0D; Method: A retrospective cohort study implementing a quantitative, descriptive and analytical approach developed in two public teaching hospitals located in the Central-West region of Brazil, from November 2010 to October 2011. Data collection was performed through medical records of 32 patients with SCA to assess clinical and hematological parameters before and after HU treatment. The study was approved by the UFMS Ethics Committee under protocol number 1890/2010.&#x0D; Results: All of the 32 patients were homozygous with a mean age in the prescription of hydroxyurea of 19.72±7.58 years, an initial dose of 15.59±4.27 mg/kg/day, and 22.48±5.35 mg/kg/day in the fourth year of treatment. Regarding the use of HU, average values of some hematological parameters presented a significant difference in the fourth year compared to the mean values prior to HU use, such as fetal hemoglobin (14.49±7.52%), red blood cells (2.54±0.38x1012/L), hematocrit (25.30±4.03%) and hemoglobin (9.22±3.34g/dL). &#x0D; Conclusion: Treatment with hydroxyurea showed a significant increase in fetal hemoglobin levels, increased hemoglobin, hematocrit and average corpuscular hemoglobin concentration, with reduced episodes of pain, infection and acute chest syndrome in such a way as to reaffirm its efficiency in treating these patients.&#x0D; Keywords: Hemoglobin; Sickle Cell Anemia; Hydroxyurea.

Influence of glucose-6 phosphate dehydrogenase (G6-PD) deficiency upon clinico-haematological and biochemical expression of patients with sickle cell disease

Background: According to world health organization, G6PD deficiency constitute 7.5% of world population as carriers whereas 2.9% as deficient. It has been reported from India that the prevalence varies from 0-27% in different caste, ethnic and linguistic groups. Various studies have revealed strong interaction between G6PD deficiency and sickle cell genes on one hand and environment on the other, one may therefore expect changes in their frequencies over a period of time in the population. We studied the influence of G6PD deficiency upon the clinico-haematological and biochemical expression of sickle cell disease.Methods: The study was carried out prospectively from September 2010 to August 2011 in the department of Pathology at our institute. The material for the present study consisted of 100 cases including 76 patients with Sickle cell disease and 24 of control group. On all the samples after screening and confirmatory tests, hematological and biochemical tests were performed and discussed along with their clinical profiles.Results: A total of 100 patients were studied, 76 were of sickle cell disease and remaining 24 patients were of control group. Majority of sickle cell trait (AS) patients (55.6%) and control patients (54%) had mild anaemia while most of the sickle cell anemia (SS) patients (44.4%) had moderate anaemia. The 2 (100%) AS and 1 (100%) control G6PD deficient patients had moderate anemia while the 2 (100%) SS patients with G6PD deficiency had severe anemia. All the sickle cell disease and control patients with G6PD deficient had elevated serum bilirubin and in all of them only unconjugated bilirubin was raised. None of the SS patients were asymptomatic. All the G6PD deficient patients had pallor and icterus. Vaso-occlusive crisis, acute chest syndrome and infectious episode were present in one (50%) each of AS and SS patients with G6PD deficiency.Conclusions: G6PD deficiency neither exacerbated nor mitigated the frequency of painful crisis, incidence of infection or anemic episodes in patients with sickle cell disease. Hematologically no significant differences were observed in sickle cell disease patients (AS and SS) with G6PD deficiency as compared to sickle cell disease patients without G6PD deficiency and the control.

Low Nocturnal Hemoglobin Oxygen Saturation Does Not Predict Pain or Acute Chest Syndrome Episodes in Children with Sickle Cell Anemia

Background: Previous evidence has shown that low mean nocturnal oxyhemoglobin saturation is significantly associated with a higher number of pain days per year Hargrave et al. (Blood. 2003; 101(3)846-8). We tested the primary hypothesis that sleep disordered breathing, described by low mean nocturnal oxygen saturation (SpO2), is associated with increased rates of severe vaso-occlusive pain and acute chest syndrome (ACS). Our secondary hypothesis investigated the association between high obstructive apnea hypopnea index (OAHI; the number of obstructive apneas and hypopneas with >3% SpO2desaturations or arousals per hour of sleep) with increased incidence of severe pain requiring hospitalization and ACS episodes.Study design: A prospective cohort study of children and adolescents from the Sleep and Asthma Cohort (SAC) was assembled. Children with sickle cell anemia (SCA), defined as HgbSS or Hb Sβ°, were enrolled from 4 to 18 years of age at three clinical centers, Washington University School of Medicine in St. Louis, Missouri; Case Western Reserve University in Cleveland, Ohio; and University College London in London, UK (which recruited from three London hospitals). At each site, SAC study-certified technicians performed full 12 channel in-laboratory research polysomnography (PSG) including continuous measurements of nocturnal oxygen saturation using standardized protocols according to American Academy of Sleep Medicine guidelines for data acquisition and scoring. All PSGs were read centrally at Vanderbilt University School of Medicine. Negative binomial regression was used to test the association between nocturnal SpO2 and the incidence rate of severe pain requiring hospitalization and ACS episodes. Covariates in the primary models for pain and ACS included: age at polysomnography, sex, hemoglobin, white blood cell count (WBC), OAHI, and mean nocturnal SpO2. All covariates meeting a significance criteria of p<0.20 were subsequently included in the final model for pain or ACS. Pain rate was defined as number of vaso-occlusive pain events that required hospitalization per year. ACS event was defined as an episode of acute respiratory distress associated with a new radiodensity on chest roentgenogram and at least one of the following: temperature greater than 38° Celsius, increased respiratory effort, decreased oxygen saturation, or increased respiratory rate documented in the medical record. A diagnosis of pneumonia was considered an ACS episode. If a pain event occurred with an ACS episode, the participant was counted as having an ACS event.Results: A total of 252 participants with SCA underwent polysomnography and after quality control, 243 were included; of these 223 had values for pain and ACS after polysomnography; missing data were due to lack of follow-up. Of the 223 participants, 18 on hydroxyurea therapy at the time of PSG and one with missing hydroxyurea status were excluded in primary analyses as hydroxyurea treatment is known to significantly influence pain incidence. The final sample included 204 participants, median age 10.4 years (interquartile range 7.3). Participants were followed for median 5.0 years (interquartile range 1.8 after PSG). After adjusting for age, sex, WBC, and hemoglobin, higher nocturnal SpO2 was associated with increased incidence of pain, which is in the opposite direction of our hypothesis (incidence rate ratio 1.11, 95% CI 1.06-1.17, p<0.001). Mean nocturnal SpO2 was not associated with ACS (incidence rate ratio 1.02, CI 0.96-1.09, p=0.500). In separate models, adjusting for age, sex, WBC, and hemoglobin, OAHI was not associated with future pain using either the log OAHI (IRR 0.99, CI 0.88-1.10, p=0.805) or with OAHI ≥2 (IRR 0.87, CI 0.55-1.41, p=0.569). After adjustment for covariates, OAHI was not associated with ACS using either the log OAHI (IRR 1.06, CI 0.92-1.21, p=0.450) or with OAHI ≥2 (IRR 0.86, CI 0.53-1.39, p=0.541). In an attempt to replicate the Hargrave analysis (Blood. 2003; 101(3)846-8), we investigated whether pain days per year was associated with nocturnal SpO2. Nocturnal SpO2was associated with pain days per year, but in the opposite direction of our hypothesis (IRR 1.12, 95% CI 1.05-1.20, p= 0.001).Conclusion: In an unselected group of children with SCA, low mean nocturnal SpO2 and elevated OAHI are not associated with clinically relevant increased incidence rates of vaso-occlusive pain or ACS. DisclosuresNo relevant conflicts of interest to declare.

Update from the Hgb-205 Phase 1/2 Clinical Study of Lentiglobin Gene Therapy: Sustained Clinical Benefit in Severe Hemoglobinopathies

Introduction: β-globin gene transfer into hematopoietic stem cells (HSCs) has the potential to reduce or eliminate the symptoms of severe sickle cell disease (SCD) and reduce or eliminate transfusion requirements in transfusion-dependent β-thalassemia (TDT). LentiGlobin Drug Product (DP) contains autologous CD34+ cells transduced with the BB305 lentiviral vector, which encodes a human β-globin gene containing a single point mutation (AT87Q) designed to confer anti-sickling properties similar to those observed with γ-globin. We previously reported proof of concept for LentiGlobin DP treatment in severe SCD and early data from 4 treated patients with TDT. We now report 18 months of follow-up for the patient with SCD and between 9 and 30 months of follow-up for the 4 patients with TDT.Patients (5-35 years of age) with severe SCD (e.g. ≥2 acute chest syndrome episodes or ≥2 vaso-occlusive crises [VOC] in preceding year/in year prior to regular transfusions) or TDT (≥100mL/kg of packed red blood cells [RBCs] per year) were enrolled. Following mobilization and apheresis (for TDT) or bone marrow harvest (for SCD), autologous CD34+ cells were transduced with the BB305 lentiviral vector. Patients underwent myeloablative conditioning with busulfan prior to infusion of the transduced cells. After infusion, patients were monitored for hematologic engraftment, vector copy number (VCN), and HbAT87Q expression. Disease-specific assessments included transfusion requirements for TDT, or VOCs and hospitalizations for SCD. Safety assessments included adverse events (AEs) and integration site analysis.Results: As of July 2016, 1 patient with severe SCD (male; 13 years old) and 4 patients with TDT (2 male, 2 female; 16-19 years old) have received LentiGlobin DP in Study HGB-205. The median LentiGlobin DP cell dose was 8.9 (range 5.6-13.6) x 106 CD34+ cells/kg with a DP VCN of 1.2 (range: 0.8-2.0) vector copies/diploid genome. Median post-infusion follow-up as of July 6, 2016 is 20.8 months (range 9.5-31.3). All subjects successfully engrafted after receiving LentiGlobin DP, with a median time to neutrophil engraftment of 17 days (range 14-38 days). VCN in peripheral blood has remained generally consistent from Month 3 in all patients with a range of 0.2 to 3.4 at last measurement. The toxicity profile observed from start of conditioning to latest follow-up remains consistent with myeloablative conditioning with single-agent busulfan, with no DP-related ≥Grade 3 AEs or serious AEs and no evidence of clonal dominance reported to date.Three patients with TDT have β0/βE genotypes and 1 is homozygous for the severe β+ mutation IVS1 nt 110 G>A. The 2 patients who have completed the 2-year primary follow-up period (both β0/βE) have not required RBC transfusions for 31 and 28 months, with total Hb of 10.9 and 13.5 g/dL, and HbAT87Q expression of 7.7 and 10.1 g/dL, respectively, at most recent study visit. Iron chelation has been discontinued and phlebotomy initiated for 1 of the patients. The remaining patient with β0/βE genotype has 9 months of follow-up and has not required transfusions since 4 days post-LentiGlobin DP infusion, achieving a total Hb of 11.3 g/dL at last study visit. The patient with the severe IVS1 genotype has 12 months of follow-up and has been free of transfusions for 9 months, with a total Hb of 8.3 g/dL at last study visit.The patient with severe SCD, who prior to study enrollment received regular RBC transfusions, has experienced no clinical symptoms or complications of SCD in the 18 months since treatment, despite discontinuing transfusions 3 months after LentiGlobin DP infusion. Total Hb in this patient was 12.5 g/dL, with 6.6 g/dL HbAT87Q (53%) and 5.7 g/dL HbS (45%) at last study visit. Compared with values at screening, unconjugated bilirubin had dropped 78% (50 to 11 μmol/L), lactate dehydrogenase had dropped 54% (626 to 287 U/L), and reticulocyte count had dropped 45% (238x109/L to 132x109/L) by Month 18.Conclusions: Data from this ongoing Phase 1/2 clinical study suggest that treatment with LentiGlobin DP can result in sustained production of therapeutic HbAT87Q, which ameliorates the clinical and biochemical effects of severe SCD and TDT, with an acceptable safety profile. Gene therapy presents a potentially promising therapy for patients with severe hemoglobinopathies. Further follow-up and additional data from patients are needed to confirm the encouraging results seen to date in this study. DisclosuresRibeil:Bluebirdbio: Consultancy; Addmedica: Research Funding. Payen:bluebird bio: Patents & Royalties. Hermine:Alexion: Research Funding; Celgene: Research Funding; Novartis: Research Funding; AB science: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau. Asmal:bluebird bio: Employment, Equity Ownership. Joseney-Antoine:bluebird bio: Employment, Equity Ownership. De Montalembert:Addmedica: Research Funding; Novartis: Research Funding, Speakers Bureau. Leboulch:bluebird bio, Inc: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Prospective Implementation of Multi-Disciplinary Obstetric Team Decreases the Mortality Rate of Pregnant Women with Sickle Cell Disease in Ghana

Prospective Implementation of Multi-Disciplinary Obstetric Team Decreases the Mortality Rate of Pregnant Women with Sickle Cell Disease in Ghana

Cardiopulmonary Fitness and Clinical Outcomes in Adults Followed in the Cooperative Study for Sickle Cell Disease

Introduction: Cardiopulmonary fitness is significantly reduced among individuals with sickle cell disease (SCD). Cardiopulmonary fitness is also an important predictor of morbidity and all-cause mortality in the general population. However, the relationship between fitness and clinical outcomes in SCD has not been well studied. The objectives of this analysis were to: 1) determine the factors associated with fitness in a cohort of adults with SCD, and 2) evaluate the relationship of fitness to hospitalization for pain and acute chest syndrome (ACS) and overall mortality. We hypothesized that clinical factors such as age, sex, hemoglobin, SCD genotype and cardiopulmonary disease significantly affect fitness, and that poor fitness is a predictor of more frequent hospitalizations for pain and ACS and higher mortality in adults with SCD.Methods: A cohort of adults with SCD was constructed from participants enrolled in phase 2 of the Cooperative Study of Sickle Cell Disease (CSSCD) who underwent exercise testing (modified Balke treadmill protocol). Primary measure for fitness was total treadmill duration. Retrospective pain or ACS hospitalization rates were calculated using events in the 3 years prior to exercise testing. Mortality and prospective hospitalization rates for pain and ACS were calculated using events after exercise testing with a minimum 6 month follow-up. Results of pulmonary function testing (PFT), echocardiography, and laboratory testing within 3 years of exercise testing were included in our analysis. Standard descriptive analyses were performed (SPSS V24). Multivariable negative binomial and Cox proportional hazards models were constructed to evaluate the relationship of fitness to ACS and pain hospitalization rates and mortality, respectively. Multivariable linear models were constructed to determine factors associated with fitness.Results: A total of 223 participants had valid exercise testing data (64% female, 70% hemoglobin SS or S/b0 thalassemia, mean age 43.3 ± 7.5 years, mean hemoglobin 9.1 ± 2.2 g/dl, mean follow-up 2.7 ± 0.7 years after exercise testing). Participants completed a mean of 11.6 ± 5.2 min on the treadmill, with 87% completing ≥ 3 stages but only 17% completing all 10 stages. We categorized fitness into tertiles of treadmill duration (5.7 vs. 11.8 vs. 18.1 min, p < 0.001). Age (45.2 vs. 43.1 vs. 41.3 years, p = 0.007), baseline hemoglobin (8.5 vs. 9 vs. 9.8 g/dl, p = 0.003), as well as the proportion of females (77 vs. 71 vs. 40%, p < 0.001) and participants with abnormal PFT (58 vs. 35 vs. 39%, p = 0.008), differed significantly across fitness tertiles. Pain or ACS hospitalization rates during the 3 years prior to exercise testing were not significantly different across fitness tertiles. Using multivariable linear regression, male sex (β = 3.1, p < 0.001), lower age at exercise testing (β = -0.14, p = 0.003), and higher hemoglobin (β = 0.44, p = 0.049) were independently associated with higher fitness, with abnormal PFT trending toward significance (β = -1.28, p = 0.07). In this model, genotype, tricuspid regurgitant jet velocity (TRJV) ≥ 2.5 m/s, and pain and ACS hospitalization rates prior to exercise testing were not significantly associated with fitness. Using a negative binomial regression model, we found that fitness did not predict future pain or ACS episodes after adjustment for age, sex, genotype, hemoglobin and TRJV. Fitness also did not predict survival in our cohort (hazard ratio, 0.97; 95% CI [0.84, 1.13], p = 0.71), in which death was reported in only 9 participants. In our Cox regression model, male sex (HR 7.1; 95% CI [1.3, 38.9]; p = 0.02) and lower hemoglobin (HR 0.56; 95% CI [0.36, 0.88]; p = 0.01) were independent predictors of death, but age at exercise testing, abnormal PFT and TRJV ≥ 2.5 m/s were not.Conclusions: In adults with SCD, lower fitness is significantly associated with female sex, older age, lower hemoglobin and abnormal PFT. Fitness did not predict survival or future pain or ACS events in the CSSCD. Given that cardiopulmonary fitness remains an important predictor of all-cause mortality in the general population, larger scale prospective studies in SCD are needed to evaluate the impact of regular exercise on improving fitness, quality of life, clinical outcomes and mortality in this population. DisclosuresBadawy:Ann & Robert H. Lurie Children’s Hospital of Chicago: Employment; Ann & Robert H. Lurie Children’s Hospital of Chicago: Research Funding; Salveo Health Communications LLC: Consultancy. Payne:National Center on Birth Defects and Developmental Disabilities: Employment. Liem:Ann & Robert H. Lurie Children’s Hospital of Chicago: Employment; Ann & Robert H. Lurie Children’s Hospital of Chicago: Research Funding; National Institute of Health: Research Funding.

A trial of unrelated donor marrow transplantation for children with severe sickle cell disease

AbstractChildren with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), ≥3 vaso-occlusive pain crises per year (n = 12), or ≥2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials.gov as #NCT00745420.

Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype.

Current definitions of acute chest syndrome (ACS) in sickle cell anemia (SCA) do not account for rapid progression of respiratory compromise. In this two-center retrospective cohort study, we tested the hypothesis that in children and adults with ACS and respiratory failure (≤24 hours after onset of respiratory symptoms) have a distinct ACS phenotype associated with multiorgan failure when compared to those with ACS that have a more subacute and protracted course. We identified 173 individuals (97 children <20 years and 76 adults ≥20 years) with SCA and at least one episode of ACS. Only one ACS episode was considered per individual. Rapidly progressive ACS occurred in 21% (n = 16) of adults, but only 2.1% (n = 2) of children. Compared to adults without rapidly progressive ACS, adults with rapidly progressive ACS more frequently developed acute kidney injury (68.8% vs. 3.3%, P < 0.001), hepatic dysfunction (75.0% vs. 15.0%, P < 0.001), altered mental status (43.8% vs. 11.7%, P < 0.001), multiorgan failure (93.8% vs. 10%, P < 0.001), and death (6.3% vs. 0%, P = 0.05). Clinical and laboratory covariates that were evaluable on the first day of respiratory symptoms were evaluated to identify predictors of rapidly progressive ACS. On multivariable analysis, decline in platelet count at presentation was the only predictor of rapidly progressive ACS [odds ratio 4.82 (95% CI 1.20-19.39), P = 0.027]. In conclusion, rapidly progressive ACS is a distinct phenotype that occurs more frequently in adults, is preceded by thrombocytopenia, and is associated with multiorgan failure. Am. J. Hematol. 91:1185-1190, 2016. © 2016 Wiley Periodicals, Inc.

Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. To assess the benefits and risks associated with the use of bronchodilators in people with acute chest syndrome. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2002) and Embase (1981 to 2002).Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 11 July 2016. Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.

Pattern of Lung Function Is Not Associated with Prior or Future Morbidity in Children with Sickle Cell Anemia.

Patient factors associated with development of abnormal lung function in children with sickle cell anemia (SCA) have not been fully characterized. To characterize lung function abnormalities among children with SCA and to determine whether these steady-state lung function results were associated with morbidity before or after testing among children with SCA. This study was part of the prospective National Institutes of Health-funded Sleep and Asthma Cohort Study. Children with HbSS or Hb Sβ(o) (SCA) were enrolled without regard for sickle cell-related comorbidities or diagnosis of asthma. Lung function was measured by spirometry and plethysmography on the same day, when free of acute disease. Standardized asthma symptom questionnaires and review of the medical records were also performed. A total of 149 children aged 6 to 19 years completed lung function testing, of whom 139 participants had retrospective morbidity data from birth to the test date, and 136 participants were followed prospectively for a median of 4.3 years from the test date. At baseline, percentages with normal, obstructive, restrictive, nonspecific, and mixed lung function patterns were 70, 16, 7, 6, and 1, respectively. Neither retrospective rates of pain nor acute chest syndrome was associated with lung function patterns. Furthermore, baseline lung function pattern was not predictive of future pain or acute chest syndrome episodes. The majority of children with SCA have lung function that is within the normal range. Abnormal lung function patterns were not associated with prior vasoocclusive pain or acute chest syndrome episodes, and baseline lung function patterns did not predict future vasoocclusive pain or chest syndrome episodes.

Hydroxyurea Effectiveness in Children and Adolescents with Sickle Cell Anemia: A Large Retrospective, Population-Based Cohort Study

Background: The clinical efficacy of hydroxyurea (HU) in patients with sickle cell anemia (SCA) is well established. In clinical trials, HU has been demonstrated to alter the clinical course of SCA; HU decreases rates of pain, dactylitis, acute chest syndrome (ACS), transfusions, hospitalizations and improves hemoglobin levels. Other studies have shown that HU improves quality of life and decreases mortality. While evidence of efficacy has been well demonstrated, published data about clinical effectiveness is limited. Additionally, attempts to compare outcomes of patients taking HU to those not taking HU have been limited by the inherent selection bias for greater disease severity in patients on HU. We sought to examine the clinical effectiveness of HU in the large population of patients with sickle cell disease (SCD) at Children's Healthcare of Atlanta (CHOA). The program provides comprehensive care to >1,700 active patients; because they include about 95% of all children and adolescents with SCD in the greater Atlanta Metropolitan Area, the program provides a population-based sample. Currently 57% of the 922 children ≥ 1 yr of age with SCA (SS and Sβ0 thalassemia) who are not on chronic transfusions are receiving HU.Methods: Using a retrospective cohort, pre-post treatment study design to control for disease severity selection bias we evaluated the clinical effectiveness of HU in patients with SCA who received care at CHOA and who first initiated HU in 2009-2011. Children on chronic transfusions, or children with inadequate follow up data and/or who ever took HU in the 3 years prior were excluded. Clinical guidelines for dosing HU have been standardized locally and recommend initial dosage of 20mg/kg/day, followed by dose escalation every 2 months to maximum tolerated dose. For each patient, healthcare utilization, laboratory values and clinical outcomes for the 2-year period prior to HU initiation were compared to those for two years after initiation. Medians were compared using the Wilcoxon Signed Rank test and means using T test. Rate ratios were computed using unadjusted Poisson regression. Interactions testing whether the effect of HU varied by age, sex, or insurance status, were assessed using multivariable Poisson regression.Results: Of 211 children with SCA who initiated HU in 2009-2011, 134 met eligibility criteria. After initiation of HU, the rate of hospitalization was 0.53 the rate before HU, a 47% reduction (Table). The number of inpatient days, emergency room (ER) visits, pain encounters, episodes of acute chest syndrome (ACS), and transfusions were also significantly reduced (Table). The hemoglobin level (mean +/- SD) pre- and post-HU initiation was 7.3+/-2.7 g /dl and 8.1+/- 2.9 respectively; an increase of 0.8+/-1.1, p<0.0001. Similarly, pre-HU mean corpuscular volume increased from 82.9+/-7.5 fl pre-HU to 95.7+/-10.7 post-HU; an increase of 12.8+/-7.2, p <0.0001. There was a statistically significant interaction between the effect of HU and age of initiation of the drug on hospitalization rates; patients < 7 years of age had a greater reduction in hospitalizations than older children (58% vs 33%, p=0.03). The effect of HU on hospitalizations did not vary by sex or insurance type.Table 1Effect of HU initiation on clinical outcomes using Poisson RegressionRate Ratio (Confidence Limits)P ValueHospitalizations0.53 (0.43 - 0.66)<0.0001Inpatient Days0.50 (0.40 - 0.63)<0.0001ER visits0.57 (0.49 - 0.67)<0.0001Pain Encounters0.64 (0.51 - 0.81)0.0001ACS0.57 (0.39 - 0.83)0.0036Blood Exposure0.43 (0.29 - 0.64)<0.0001Conclusions: HU is clinically effective in children and adolescents with SCA. HU decreased hospitalizations, ER visits, pain encounters, ACS, use of transfusions and improved hemoglobin levels. HU effectiveness was similar across gender, insurance types and age, although there was a slightly greater reduction in hospitalizations in younger patients. These results are important as they parallel results obtained from HU efficacy studies, thus demonstrating that in 'real life' settings, even without the additional monitoring and adherence incentives of clinical trials, HU improves short-term outcomes in pediatric SCA. DisclosuresOff Label Use: Hydroxyurea use as disease modifying therapy in pediatric patients with sickle cell disease.

Results of a Multicenter Pilot Investigation of Bone Marrow Transplantation in Adults with Sickle Cell Disease (STRIDE)

▪Background: Hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) is potentially curative, yet applied sparingly in adults due in part to limited donor availability and to concerns about safety. We conducted a multicenter pilot clinical trial to determine ways to broaden the availability of this therapy.Objective: To determine the feasibility, efficacy, and safety of a reduced toxicity transplant conditioning regimen in adults with severe SCD receiving related and unrelated donor HCT.Methods: Patients between 16-40 years of age were enrolled between October 2012 and June 2015 at 8 participating transplant centers. Eligibility criteria included stroke; recurrent episodes of acute chest syndrome (ACS) or sickle pain in the past 2 years; 8 or more RBC transfusions/year; or a tricuspid valve regurgitant jet velocity ³2.7 m/sec. Patients received unmodified bone marrow from a human leukocyte antigen (HLA)-matched sibling or an unrelated donor matched for 8 of 8 HLA loci. Patients were prepared for HCT with Busulfan from day -8 to -5 (13.2 mg/kg), Fludarabine from day -7 to -3 (150 mg/m2) and Thymoglobulin from day -5 to -2 (6 mg/kg). GVHD prophylaxis consisted of cyclosporine or tacrolimus with methotrexate.Outcomes and Measures: The primary endpoint was event-free survival 1 year after HCT, with events defined as graft failure, disease recurrence, or death. The Kaplan-Meier probabilities of event-free and overall survival were determined. Donor chimerism, transplant-related toxicities and clinical and laboratory measures of SCD were secondary endpoints obtained 1 year after HCT. Serious adverse events were monitored after transplantation.Results: Twenty-two patients (13 were female) who ranged in age from 17-36 (median 22) years were enrolled. Seventeen patients received a sibling and 5 an unrelated donor HCT. An eligibility review committee confirmed subject eligibility. Enrolled subjects had stroke (2 pts), ACS (3 pts), painful crises (14 pts), RBC transfusions (6 pts) and/or tricuspid valve regurgitant jet velocity (5 pts); 8 subjects satisfied eligibility criteria for more than 1 category. There were 6 severe adverse events after transplantation in 4 patients including one death from intra-cranial hemorrhage related to posterior reversible encephalopathy syndrome. None of the patients had graft failure or SCD recurrence after HCT. Currently, 21 of 22 patients survive with stable engraftment of donor cells at a median 9.7 months (range, 1-31) after HCT. The overall and event-free survival probabilities are both 95% (90% CI 76%; 99%, Figure 1) at 12-months after HCT. Two patients developed grade I skin acute GVHD and three patients developed chronic GVHD. Full donor myeloid chimerism was observed after HCT. The median donor T-cell and RBC chimerism at 28, 100 and 180 days after HCT was 55.5% and 100%, 80% and 100%, and 87.5% and 100%, respectively.Conclusions: We report excellent outcomes after HLA-matched HCT in adults with SCD using a reduced toxicity-conditioning regimen performed in a multi-center setting. We observed very low rates of graft rejection and GVHD in this pilot study. We speculate that these outcomes, if sustained long-term after HCT, will be superior to survival in adults with SCD who receive standard supportive care. If confirmed in a larger comparative trial, this approach would broaden the availability and application of transplantation for adults with severe SCD. [Display omitted] DisclosuresWalters:ViaCord and AllCells, Inc: Other: Medical director.

Acute Kidney Injury Is Prevalent Among Pediatric Admissions for Acute Chest Syndrome

Background: Growing evidence shows that acute kidney injury (AKI) leads to chronic kidney disease in pediatric and adult populations. Patients with sickle cell disease (SCD) that develop acute chest syndrome (ACS) are at risk for developing AKI due to the hypoxic, acidic environment in the renal medulla, the use of nephrotoxic agents (vancomycin, NSAIDs), hyposthenuria and potential dehydration experienced by patients prior to admission for ACS. As AKI and acute lung injury are linked by systemic organ cross-talk, AKI with or without oliguria, may exacerbate the pathologic state of ACS. For these reasons, improving our understanding of the epidemiology and pathophysiology of AKI during sickle cell crisis is paramount.Methods: We conducted a six year retrospective observational evaluation of 236 episodes of ICD-9 defined ACS among 166 admitted pediatric patients. We excluded patients admitted for one day or had normal CXR throughout hospitalization despite being coded as ACS. AKI was defined by KDIGO definition of either a ≥ 0.3 mg/dL or 50% increase in serum creatinine (SCr) from baseline. Forty eight episodes were excluded as a baseline SCr was not identified. Variables analyzed included age, gender, SCD genotype, length of stay, CBC (baseline and admission), current SCD therapy, transfusion intervention and length of stay (LOS). Per institutional standard of care, patients with ACS are treated with Vancomycin, Azithromycin, and Ceftriaxone and receive NSAIDS (ibuprofen or toradol) for pain/fevers but the type/timing of transfusion is determined by SCD provider preferences. Logistic regression analysis was performed to assess associations between clinical variables and AKI for all patients and severe phenotypes. Multiple linear regression analysis was performed to determine if AKI was independently associated with hospital length of stay.Results: The mean age of patients admitted with ACS was 9 years (range 0.8yrs-19) and 61% were male. Genotypes included SS (79%) SB0 thalassemia (4%), SB+ thalassemia (5%), SC (12%) and SD (1%). AKI was identified in 13 of 188 (7%) episodes of ACS. The majority of cases developed AKI within two days of admission and resolved 2.5 days later. Compared to children without AKI, those with AKI had a lower admission hemoglobin (6.3 vs 7.5 g/dL, p=0.02), lower decrease in hemoglobin from baseline (3.2 vs. 1.3 g/dL, p<0.001), and higher admission WBC (32.3 vs. 20.3 x103/uL, p<0.001). Finally, need for exchange transfusion was associated with AKI (χ2 = 9.8, p=0.007). Seven of 39 patients (18%) that underwent exchange transfusion, 5 of 137 (4%) simple transfusion patients, and 1 of 16 no transfusion patients (the one patient had severe RBC antibodies so was not transfused) developed AKI. The patients with and without AKI were similar for age, gender, SCD genotype, platelet count, and current SCD therapy. When evaluating whether AKI was associated with longer LOS, we found that those with AKI had longer LOS than those without (12.4 vs 5.0 days, p<0.001). Using nominal logistic regression, drop in hemoglobin from baseline (p<0.001), admission WBC (p=0.01), and length of stay (p<0.001) remained significantly associated with AKI (Χ2 =42, p<0.001). When excluding patients with milder SCD phenotypes (SC and SB+ thalassemia), similar results were observed. Among 164 ACS events with severe SCD genotypes, 11 (14%) patients developed AKI. Using nominal logistic regression to assess severe SCD genotypes, drop in hemoglobin, admission WBC, and LOS were significantly associated with the development of AKI (Χ2=36, p<0.001).Conclusion: This study demonstrates that AKI is prevalent during admissions for ACS and is highly associated with a drop in Hb and increase in WBC on admission and the need for exchange transfusion. While AKI presented and resolved early during hospitalization, it is strongly associated with a prolonged hospital course. The impact of AKI on the pathophysiology of ACS in the acute setting as well as its role in progression to SCD nephropathy should be studied prospectively. DisclosuresNo relevant conflicts of interest to declare.

Benefits of Patient-Controlled Analgesia without Continuous Infusion for the Treatment of Sickle Cell Disease Vaso-Occlusive Crisis Pain

Introduction: Sickle cell disease (SCD) is a chronic illness characterized by unpredictable episodes of pain, cumulative organ damage, and high-health care utilization rates. Intravenous opioids are considered a mainstay in the management of acute vaso-occlusive pain crisis (VOC). In 2007, van Beers and colleagues demonstrated that the use of patient-controlled analgesia (PCA) results in significant reductions in morphine consumption with equivalent response on measurements of pain and quality of life, and this is largely accepted by SCD providers. There remains controversy regarding the method of administration of opioids via PCA, with studies examining varying ratios of continuous to demand dosing. PCA with basal infusion plus demand dosing seems to be preferred by the hematology community whereas emerging data in other populations, demonstrate adequate pain control and reduced rates of opioid-related adverse events with the use of demand only approaches. In October 2012, as part of a quality improvement initiative at the Children's Hospital at Montefiore, we revised our pain management guidelines to exclude the routine use of basal infusions in our PCA protocol. In addition, pain management consultation was requested to assist in management of PCA, particularly as it related to the appropriate use of basal infusions when indicated and timely transition to oral analgesics. Short-term methadone during the inpatient stay with a short taper post discharge was utilized for improved and long-acting analgesia in patients that did not improve rapidly on the standard regimen.Methods: We conducted a retrospective analysis of patients with SCD < 21 years of age, admitted for VOC 3-7 times/year, comparing patient admissions in 2011 versus 2013, pre- and post-revision of the pain protocol as described above. Baseline variables evaluated include demographic and clinical characteristics outlined in Table 1. Primary outcomes include total opioid utilization during inpatient admission, total hours on intravenous PCA and length of stay (LOS). Secondary outcomes include rates of acute chest syndrome, hypoxia, exchange transfusion and transfer to the pediatric intensive care unit.Results: A total of 144 admissions were included in the analysis, 73 in 2011 and 72 in 2013. Baseline demographics and clinical characteristics were similar in both groups (Table 1). In 2011, 72/73 patient admissions were treated with PCA with basal infusion compared to only 1/72 patient in 2013. Total opioid utilization during inpatient admission, total PCA hours and LOS were significantly reduced in the 2013 group compared to the 2011 group with no significant difference in admit pain to discharge pain (Table 2). Furthermore, patients in the 2013 group demonstrated a significantly lower incidence in episodes of hypoxia and acute chest syndrome (Table 2)Conclusions: In conclusion, we demonstrate the feasibility and benefits of demand only PCA in the management of VOC pain. Superiority of the demand only PCA approach needs to be rigorously evaluated in a randomized prospective study.Table 1Baseline demographic and clinical characteristics by admissions:2011 (n=73)2013 (n=72)P-valueAge (years)16.3 ± 3.515.4 ± 3.30.40Gender M F39 (53.4%) 34 (46.6%)32 (44.4%) 40 (55.6%)0.62Race Black Multiracial60 (82.2%) 13 (17.8%)61 (84.7%) 11 (15.3%)0.87Ethnicity Non-Hispanic Hispanic55 (75.3%) 18 (24.7%)55 (76.4%) 17 (23.6%)0.85Genotype Hbg SS Hgb SC68 (93.2%) 5 (6.8%)59 (81.9%) 13 (18.1%)0.18Weight (kg)57.3 ± 17.654.7 ± 19.30.45Opioid tolerant Y N9 (12.3%) 64 (87.7%)3 (4.2%) 69 (95.8%)0.25Hydroxyurea Y N44 (60.3%) 29 (39.7%)33 (45.8%) 39 (54.2%)0.50Hemoglobin (g/dL)8.7 ± 1.88.6 ± 1.60.85HgbS % HgbF%77.5 ± 10.410.9 ± 6.977.7 ± 15.16.5 ± 5.60.97 0.10Table 2Comparison of primary and secondary outcomes by admissions:2011 (n=73)2013 (n=72)P-valueTotal opioid utilization during inpatient admission* (mg IV ME/kg**)13.3 ± 33.83.6 ± 3.00.0003Total PCA hours153.2 ± 103.280.0 ± 45.4<0.0001Length of stay (days)7.5 ± 5.05.5 ±7.40.002Change in pain score (Admit pain to discharge pain)5.5 ± 3.15.7 ± 3.20.82Hypoxia21/73 (28.8%)5/72 (6.9%)0.0008Acute chest syndrome16/73 (21.9%)2/72 (2.8%)0.0043*all oral and IV opioids were included**mg IV ME/kg = milligrams of intravenous morphine equivalents per kilogram DisclosuresNo relevant conflicts of interest to declare.