Information about age of death, cause of death, and related factors among those living with sickle cell disease (SCD) is typically limited to data collected from a clinical setting or from single source administrative data. These methods omit individuals who did not receive care in settings that collect and publish data on their patients with SCD, or patients without SCD listed as a cause of death, respectively. CDC has implemented the Sickle Cell Data Collection (SCDC) program in California and Georgia to establish true population-based surveillance systems at the state level in an effort to address such gaps in knowledge. These data allow investigation of healthcare utilization and outcomes for patients with SCD who receive care in all settings in these states. Hospital admissions, emergency department (ED), and Medicaid claims data for the years 2004 through 2015 were obtained by the SCDC programs in both states. Patients with a SCD International Classification of Diseases (ICD) 10 code having three or more healthcare encounters within any five-year period are included in the cohort presented here; this group was linked by social security number and date of birth to the state’s death records for the same period to identify deaths. The most common causes of death (COD) were determined using the underlying COD variable and categorized based on the ICD 10 broad coding scheme. SCD COD in the death record was determined by a search of underlying COD (ICD 10 codes). In death records after 2010, additional COD were included as text strings; these were examined for SCD specific COD 2011-2015. There were 5,248 persons meeting the case definition of SCD identified in the hospital, ED, and claims data during the 12-year time frame. Of these, matching death records were found for 543 of these patients. The mean age of death for the SCD patients was 44.2 years (median 45.7 years; SD 16.0 years). As shown in Table 1, 2% percent of deaths were among children under 10 years of age, and 5.5% were among those older than 10 and less than twenty years of age. Most deaths occurred in an inpatient setting (60%), followed by home (16%), and ED/outpatient setting (15%). Similar to previous reports, SCD ICD 10 codes or text strings for additional COD or other conditions were present in only 58% (n = 160 of 275 deaths) of death reports for years 2011-2015. The ICD 10 codes for SCD were present as the underlying COD in only 36% of death reports (all years). Circulatory-related COD, which can often include terminal events such as heart failure, made up 20% of death underlying causes. Death due to external injuries or events accounted for 9% of all deaths. SCD is not reliably coded in death certificates, making mortality and associated conditions challenging to monitor at a population level. Multi-source data collection allows for population based surveillance of health outcomes for those with SCD. Abstract source

Background: Sickle cell crisis is a painful complication of sickle cell disease in adults and children. Acute episodes of severe pain (crises) are the primary reason for hospitalizations. Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified. Hospitalizations for sickle cell crisis have been steadily rising over the past decade. Though previous studies have described seasonal variations for in African and Caribbean populations, but there are no large data showing similar trends with patients in the United States. We reviewed a large national hospitalization database to determine whether rates of sickle cell crisis have seasonal variations over the past decade. Methods: We examined the Nationwide Inpatient Sample (NIS), a nationally representative survey of hospitalizations conducted by the Healthcare Cost and Utilization Project in collaboration with participating states. It is the largest all-payer inpatient dataset in the United States and includes a 20% sample of United States community hospitals that approximates 20% of all United States community hospitals. The Nationwide Inpatient Sample (NIS) database was used to estimate annual number of hospitalizations from 2000 - 2012. Identification of sickle cell disease related hospitalizations was based on the designation of the prior validated International Classification of Diseases (9th Edition) Clinical Modification (ICD-9-CM) diagnosis code 282.62 (Sickle cell crisis) as the principal discharge diagnosis. The frequency of hospitalization per month cumulative over 13 years was calculated and divided by number of days in that month to determine the mean hospitalizations per day for each month. All calculations were carried out using the weighted estimates approximating nationwide population estimates. Results: An estimated 744,072 hospitalizations with primary diagnosis of sickle cell crisis occurred in the US from 2000 to 2012. More specifically, the mean number of hospitalizations per day in each month is shown in Fig. 1. The mean number of hospitalizations each day was highest in January (2134 per day) and thereafter the hospitalization rate dropped to a nadir in June (1988 per day). There was a significant rising trend of admissions from June towards winter months with couple of peaks in September and January as depicted in the Fig. 1. In general, the number of hospitalization was maximum in the winter months and minimum in summer months as demonstrated in Fig .2. Conclusion: Contrary to expectations, we identified for the first time in United States an impressive pattern of seasonal variation in hospitalizations for sickle cell crisis with a notable increase in winter and fall and a significant drop during summer months. The seasonal pattern may reflect viral or other infections responsible for precipitation of sickle cell crisis. Otherwise, exposure to low temperatures causes increased viscosity of blood and peripheral vasoconstriction triggering sickle cell crisis. This statistical analysis calls for a definitive need to educate patients and providers on how to mitigate the adverse effects of weather on sickle cell crisis. Further efforts need to be done to identify triggers and methods to determine the relationship of these variations and reduce this predictive burden on the overall health care system. Abstract source

Background and method: This study aims to investigate on infections in sickle cell patients treated with hydroxycarbamide (hydroxyurea, HU) for symptomatic sickle-cell syndromes enrolled in the multicentric prospective non-interventional cohort study ESCORT HU (European Sickle Cell Disease COhoRT – HydroxyUrea). The first patient was enrolled in ESCORT HU in January 2009, and by June 2017, 1844 patients were enrolled in the cohort. The increased susceptibility to infections of sickle-cell disease (SCD) affected patients is well known and likely results from several causes, including impaired splenic function, defects in complement activation, micronutrient deficiencies, and tissue ischemia. Splenectomy has been considered for a long time at high risk of early and late infections and of death in children (particularly aged 4 years or below) and adults with SCD. Although antibiotics and vaccines measures have been a huge step forward in preventive care, infections remain a major cause of morbidity and mortality in the developed countries and even more so in the developing world. Hydroxyurea (HU) is registered in Europe and in the US to prevent the recurrence of painful vaso-occlusive crises including acute chest syndrome. In Europe the marketing authorization for HU covers adults, adolescents and children older than 2 years suffering from symptomatic Sickle Cell Syndrome. HU is a well-tolerated fetal hemoglobin (Hb) inducer, with dose-dependent myelosuppression being the main short-term side-effect. Concerns have been raised about the possibility of HC as a predisposing factor for infections due to its myelosuppressive property. We present here a snapshot of infections collected in SCD patients enrolled in the prospective study cohort ESCORT HU. Children (>= 2 years) and adults were enrolled from four European countries: France, Germany, Greece and Italy. Data are collected through an electronic Case Report Form (e-CRF). An analysis of these infections has been performed. Results: From January 2009 until June 2017, 1841 patients (1016 adults and 822 children) have been enrolled in ESCORT HU. 746 infections were collected in the database in 437 patients (25.5%), of which 231 children and 206 adults. Hb Genotypes were SS (89.02%) or Sβ0 (4.35%) in 408/ 437 patients (93.3%). Features of the infections are reported in table 2. Bacterial infections were reported more frequently (42.4%), followed by viral infections including parvovirus B19 (26%). In 227 cases (31%), the type of infection was not specified. The spleen status was reported sporadically. As expected, infections were more frequent in children (52.4% in children vs 46.9% in adults), despite the fact that most of them received penicillin prophylaxis. Nevertheless the number of episodes of infection per patients was quite similar between adults and children: 350 infections were reported in 206 adults (1.70 per patients) and 386 in 231 children (1.67 per patient). 60% of patients (adults as well as children) experienced one episode of infection whereas 40% reported several infections. A small number of patients (33/431) had more than 3 infectious episodes. According to the investigators, infections were more severe in adults (15.14%) than in children (8.84%), but more frequently led to hospitalization in children than in adults (34.4% vs 24.4%). Antibiotics were widely prescribed for these episodes in 77.1% (adults) and 82.6% (children) of infections. No death due to infectious episode has been reported in the cohort. Abstract source

BACKGROUND: Renal impairment is a progressive chronic complication of sickle cell disease (SCD) that begins in childhood and may progress until renal failure. It is responsible for mortality in 12% of SS SCD adults (Tehseen S, 2017). Causes of renal damages in SCD patients are multiple: hemolysis, vaso-occlusive episodes which lead to renal injuries, papillary necrosis, medullary fibrosis and focal segmental glomerulosclerosis (Rees D, 2010). Hydroxycarbamide (hydroxyurea or HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and authorized since 2007 in Europe as an orphan medicinal product for the prevention of recurrent vaso-occlusive crises and acute chest syndrome in adults and children older than 2 years with SCD. HU also seems to protect kidney function in SCD by decreasing proteinuria (Bartolucci P, 2015). As renal excretion is a pathway of HU elimination (60% of dose excreted in urine), consideration should be given to decrease the dose of HU in patients with renal impairment. We propose to study SCD patients with renal diseases treated with hydroxycarbamide (Siklos) and enrolled in ESCORT-HU (European Sickle Cell Disease COhoRT – HydroxyUrea), European multicenter prospective non interventional study. METHODS: From January 2009 to June 2017, 1841 patients were enrolled in the ESCORT-HU study. 1016 patients were adults and 824 were children (1 date of birth missing). Among them, renal lesions have been reported in the study database in 220 patients (194 adults, 25 children, 1 date of birth missing). At inclusion the renal status of patients are reported in the electronic Case Report Form (e-CRF) using different clinical approaches. It allows to distinguish patients with a medical history of renal impairment (i.e. patient with renal insufficiency of etiology not reported, with an irreversible and progressive reduction in renal function) from patients with a history of sickle cell (SC) nephropathy (patients with any renal alteration related to SCD and not necessarily irreversible and progressive). CONCLUSION: 12% of SCD patients, mainly adults, enrolled in the ESCORT-HU study had renal dysfunctions at enrolment. As expected this subpopulation is older than the global population of the cohort. Although HU is prescribed at lower doses, these patients go on to have more adverse events and this justifies a close monitoring of them. Controlled trials are required to evaluate the role of HU on the renal failure. Abstract source

HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) including acute chest syndromes in adults, adolescents and children older than 2 years with sickle-cell disease (SCD). However, based on US and European expert panel recommendations (Yawn 2014, Habibi 2015) and results from placebo-controlled clinical trials, HU could be useful in SCD patients with severe anemia without VOC since it has been demonstrated to increase total Hb level (Wang 2011) and to decrease the need for blood transfusion. We hereby present preliminary results on effectiveness and safety data related to the prescription of HU for anemia from ESCORT-HU (European Sickle Cell Disease COhoRT – HydroxyUrea), a multicentric, prospective, non-interventional European study designed to collect long-term safety data on HU in SCD population. Between January 2009 and June 2017, 1841 patients were enrolled from 63 centers in France, Germany, Greece and Italy, amongst which 126 patients (6.8%) were started on HU for anemia from 34 centers. Of these 126, 96 were HU-naive. These HU-naive patients treated for anemia (‘anemic’ subpopulation) were selected for analysis to evaluate effectiveness and safety of HU in this indication and compared with data in HU-naive patients treated for other SCD indications. Demographic data and Hb genotypes are displayed in Table 1. The mean age, distribution of gender, Hb genotype and the mean HU dose at initiation were comparable in the ‘anemic’ subpopulation and the ‘non-anemic’ HU-naive cohort. Not surprisingly, mean Hb level at initiation was markedly lower in the ‘anemic’ subpopulation (7.07 ± 0.88 g/dl) than in the ‘non-anemic’ HU-naive cohort (8.71 ± 1.51 g/dl), with a lower proportion of patients with history of VOC and SCD-related hospitalization prior to HU initiation. The mean HU dose after 6 months was comparable in both groups (15.6 ± 3.83 mg/kg/day and 15.4 ± 4.11 mg/kg/day, respectively). Abstract source

Introduction: The increased survivorship of children with sickle cell disease (SCD) into adulthood requires sufficient readiness to transition to adult healthcare. Transition readiness encompasses the necessary skills to successfully transition to adult healthcare, including self-care, decision-making (i.e., self-management), and self-advocacy. Disease education improves self-management in populations with chronic illnesses, but the relationship between disease knowledge and self-management in the adolescent SCD population during healthcare transition is unknown. We hypothesize that disease knowledge is associated with self-management and engagement in adult healthcare. Methods: Adolescents with SCD and their caregivers completed a disease self-management skills checklist (SMSC) in early adolescence. The SMSC was modified from the validated Transition Readiness Assessment Questionnaire (J Pediatr Psychol. 2011 Mar; 36(2): 160–171.). The 21-item SMSC assesses perceived disease knowledge and self-management skills. At age 17, adolescents were invited to visit adult providers prior to leaving pediatric care (J Pediatr Health Care. 2012 Nov-Dec;26(6):e45-9.) At their last pediatric visit, adolescents completed the disease knowledge quiz, which tested their actual knowledge of SCD pathophysiology and complications. The disease knowledge quiz is a new instrument with 97% content validity as assessed by six pediatric and adult SCD experts. Association of SCD knowledge and perceived caregiver and adolescent self-management skills were evaluated by Pearson correlations if normally distributed; otherwise by Spearman correlation. Univariate linear regression tested associations between disease knowledge and SMSC. Univariate logistic regression tested associations between disease knowledge, visitation to adult provider, and completion of first adult visit. Results: Thirty-six African-American adolescents (18 males; 18 females) with SCD and their caregivers completed the SMSC at a median age of 16 years and actual disease knowledge 2 years later at the last pediatric visit. Thirty-two visited adult care prior to leaving pediatrics and thirty-two completed the first adult visit. Predictors of actual adolescent knowledge immediately prior to leaving pediatrics were caregiver’s early perception of their adolescent’s self-management skills (Figure). Disease knowledge associated with higher likelihood of meeting adult providers during pediatric care (Figure). Neither self-management assessments nor disease knowledge associated with completion of first adult visit (Figure). Conclusion: Caregivers are better evaluators of their adolescent’s transition readiness than adolescent themselves, as demonstrated by a significant relationship between caregiver perceptions of their adolescent’s self-management early in the transition process and adolescents’ disease knowledge preceding departure for adult care. Adolescents’ SCD knowledge level predicted future desire to engage in adult healthcare, demonstrated by the higher likelihood of visiting adult providers while in pediatric care. The lack of relationship between self-management and disease knowledge with completion of first adult visit indicates other possible barriers curtailing successful adult care transfer. Collectively, our findings support early engagement of caregivers in measuring adolescent transition readiness to guide subsequent transition programming in the SCD population. Abstract source

Background: Acute chest syndrome (ACS) remains a leading cause of mortality among children with sickle cell disease (SCD); overall, nearly 50% of ACS is diagnosed during hospitalizations for other complications including painful vaso-occlusive crises (VOC). Methods: The present study assesses epidemiological features of children hospitalized with VOC and evaluates factors potentially associated with development of ACS utilizing the large national all-payer Kid’s Inpatient Database over a recent 9 year period. Records of children (age < 20 years) were reviewed from 2003, 2006, 2009, and 2012) and multivariable logistic regression was used to assess risk factors and adjust for patient and hospital characteristics. Results: Total annual hospitalization rates with VOC were variable, ranging from 26.4 per 100,000 children in 2009 to 29.5 in 2012. Multivariable logistic regression analysis showed children age 5-9 years had 2.38 times higher odds of developing ACS than children age 15-19 (95%CI, 2.22 to 2.56). Comorbidity of asthma was a risk factor for ACS (OR, 1.44; 95%CI, 1.36 to 1.53). ACS was as common in Hb SC patients hospitalized for VOC as those with SS. Conclusion: These data demonstrate that despite increasing use of hydroxyurea in children shown in other reports, there has been no reduction in hospitalization rate for pain, and even young children are at risk for ACS. Though de novo ACS is less common in Hb SC, vigilance and prophylactic measures are required for those hospitalized for pain. Further studies are needed to assess the efficacy of prophylactic interventions including bronchodilator therapy for asthmatics hospitalized for VOC. Abstract source

Hello. I am Dr Mary Hulihan, a health scientist in the Division of Blood Disorders at the Centers for Disease Control and Prevention. Today I would like to talk about the indications for blood transfusion in patients with sickle cell disease, the complications associated with these transfusions, and how you can help reduce the risk for these complications in your patients. For many patients with sickle cell disease, red blood cell transfusions are an important part of medical care, reducing both mortality and morbidity. Both the National Heart, Lung, and Blood Institute and the British Society for Haematology have published documents that underscore the many unique aspects of care that must be taken into account when transfusing this patient population. Although transfusions can be highly beneficial in treating sickle cell disease–related issues, they are not without risks. There are three scenarios when blood transfusions should be considered for patients with sickle cell disease. First, certain acute illnesses, such as acute chest syndrome or severe exacerbation of anemia with splenic or hepatic sequestration, may call for a simple blood transfusion. Abstract source

While acute episodic pain is the hallmark of sickle cell disease (SCD), transition to chronic pain is a major cause of morbidity and impaired quality of life. One of the core diagnostic criteria used by Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT) to define chronic SCD pain is the presence of pain on a “majority of days” in the past 6 months in one or more locations. The frequency characteristic of “majority of days” is adapted from the criteria of 15 days or more per month, used to define chronic migraine, but there are inadequate data to support this cutoff in SCD. Using an existing dataset of adults with SCD who completed patient-reported outcomes of pain interference, physical functioning, anxiety, depression, and fatigue using the National Institutes of Health (NIH) patient-reported outcomes measures information system (PROMIS) short-form instruments, we examined the association of the presence of pain on 3 or more days per week with patient-reported outcomes of functioning. In unadjusted analyses, presence of pain on 3 or more days a week was associated with higher median PROMIS scores of pain interference, anxiety, and depression. Median PROMIS scores of fatigue and physical function were worse in women compared with men in unadjusted analyses. We did not find any difference in median PROMIS pain scores between adults aged =<35 years compared with those aged >=35 years. In linear regression models, after adjustment for age and sex, the presence of pain on 3 or more days a week was found to be associated with worse pain interference and anxiety. These data support the clinical relevance of the frequency characteristic of pain on a “majority of days” in the definition of chronic SCD pain, and provide the rationale for prospective studies to validate the clinical definition of chronic pain in SCD. Abstract source Full text

BACKGROUND: Children with sickle cell anemia (SCA) are at increased risk for invasive pneumococcal disease; antibiotic prophylaxis significantly reduces this risk. We calculated the proportion of children with SCA who received ≥300 days of antibiotic prophylaxis and identified predictors of such receipt. METHODS: Children aged 3 months to 5 years with SCA were identified by the presence of 3 or more Medicaid claims with a diagnosis of SCA within a calendar year (2005–2012) in Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Receipt of antibiotics was identified through claims for filled prescriptions. The outcome, receipt of ≥300 days of antibiotics, was assessed annually by using varying classifications of antibiotics. By using logistic regression with generalized estimating equations, we estimated the odds of receiving ≥300 days of antibiotics, with potential predictors of age, sex, year, state, and health services use. RESULTS: A total of 2821 children contributed 5014 person-years. Overall, only 18% of children received ≥300 days of antibiotics. Each additional sickle cell disease-related outpatient visit (odds ratio = 1.01, 95% confidence interval: 1.01–1.02) and well-child visit (odds ratio = 1.08, 95% confidence interval: 1.02–1.13) was associated with incrementally increased odds of receiving ≥300 days of antibiotics. CONCLUSIONS: Despite national recommendations and proven lifesaving benefit, antibiotic prophylaxis rates are low among children with SCA. Numerous health care encounters may offer an opportunity for intervention; in addition, such interventions likely need to include social factors that may affect the ability for a child to receive and adhere to antibiotic prophylaxis. Abstract source Full text