Limited research had explored health care utilization (HCU) in transitioning adolescent/young adults (AYAs) with sickle cell disease (SCD). Major limitations of the current studies include the use of cross-sectional designs and lack of longitudinal exploration of HCU trajectories and the factors that might contribute to the increased HCU. The purposes of this longitudinal database study were to describe HCU trajectories of transitioning AYAs with SCD and examine factors associated with these trajectories. Methods: AYAs (12-27 years) at one urban center with a comprehensive SCD program were included if they had SCD (SS, SC, Sβ+, Sβ° genotypes) and at least two pediatric SCD clinic encounters between 01/01/1989 and 07/30/2015. We used latent class growth modeling to identify HCU (clinic, Emergency department (ED), hospitalizations) trajectories and ordinal logistic regression to examine factors associated with HCU, including individual (demographic; disease measures including severity, comorbidities, and medications), contextual (distance to clinic), and transfer-related factors (transfer age and continuity of care). We also calculated age-related ED reliance (EDR)scores. Significance was set at p<0.05. Results: 339 AYAs (55% male; 96% black; mean age=24.5 years, SD=5.38) had 10848 clinic encounters. Of these, 240 AYAs (71%) had 3840 hospitalizations and 197 (58%) had 3152 ED encounters. Low, medium, and high utilization groups were identified, with the majority of AYAs having low clinic (n=206, 60.77%), low hospital (n=171, 71.25%), and/or low ED (n=146, 74.11%) utilization trajectories (Figures 1-3). Mean age-related EDR scores were < 0.33 and increased with age (figure 4). AYAs transferred at mean age 19 and the majority had at least one additional adult clinic encounter. Factors significantly associated with higher clinic utilization trajectories included iron overload (OR=36.6; p <0.0001; 95% CI= 11.657-114.979), lower extremity ulcers (OR=8.5; p= 0.0174; 95% CI=1.457- 49.906), cerebral infarct/vasculopathy (OR=7.2; p <0.0001; 95% CI= 3.599-14.51), hydroxyurea (OR=3.2; p= 0.0007; 95% CI= 1.626-6.198), attention deficit disorders (OR=11.5; p= 0.0003; 95% CI= 3.033-43.505), and distance to clinic (OR=0.98; p <0.0001; 95%CI= 0.970-0.989). Abstract source

Introduction: Sickle cell disease (SCD) related pain is a difficult and challenging clinical problem that has significant negative effects on youth’s health-related quality of life (Dampier et al., 2010; Walco & Dampier, 1990). Proper assessment and management of pain in the pediatric population is essential to both improving wellbeing of youth with SCD, and minimizing the development of chronic pain as patients transition into adulthood. Much of the previous research on pain among youth with SCD, however, has been limited by small sample sizes, lack of comprehensive pain assessment, and failure to examine developmental differences in pain across age groups. The current study aimed to compare the expression of pain and pain interference across four developmental stages: toddlers/preschoolers (2-4 years), school-aged children (5-7 years), preadolescents (8-12 years), and adolescents (13-18 years), utilizing both parent and youth reports as appropriate (i.e., school-aged and older). We hypothesized that pain and pain interference would generally be greater among older developmental groups. Methods: The study sample included 386 youth with SCD and their parents who participated in the Sickle Cell Clinical Research and Intervention Program (SCCRIP), a longitudinal lifetime cohort study designed to examine change in health outcomes in SCD. Within SCCRIP evaluations, the Pediatric Quality of Life Inventory Sickle Cell Disease module (PedsQL; Panepinto, Torres, & Varni, 2012) is used to measure health-related quality of life including pain and pain interference. We examined the 2 pain-related subscale outcomes within the PedsQL: the Pain and Hurt and Pain Impact subscale scores in all four developmental groups. Multivariate analyses of variance (MANOVAs) were first conducted to compare, within each age group, youth- and parent-reported pain and pain interference separately. Two sample t-test or Wilcoxon rank sum test and its extended ANOVA or Kruskal-Wallis tests were then used to compare these variables depending on the normality of the data, in any two and multiple groups, respectively. Benjamini & Hochberg method was used to adjust for multiple comparisons to control for false discovery rate at an alpha level of 0.05. Results: Gender and genotype were comparable across the four developmental groups. The proportions of patient exposure to disease-modifying therapy significantly increased by developmental stage: toddler/preschool =0.50, school-aged children =0.65, preadolescents =0.63, and adolescents =0.75 (p = 0.009). Parent-reports of child pain and pain interference gradually decreased from toddlers/preschoolers to school-aged children, and then from school-aged children to preadolescents (ps ranging from <.001 to .01), but no change was observed from preadolescents to adolescents. Similarly, youth-reported pain interference gradually decreased from school-aged children to preadolescents (p = .01), and from school-aged children to adolescents (p =.035), but no change was observed from preadolescents to adolescents. No significant change in youth-reported pain was observed across developmental groups. Abstract source

Annual evaluation by Trans-Cranial Doppler (TCD) of cerebral artery blood flow is useful for determining stroke risk in children with sickle cell disease. Since the publication of the Stroke Prevention Trial in Sickle Cell Anaemia (STOP) results in 2006 it has been standard practice at our centre to perform annual TCD imaging scans on all children with sickle cell disease to identify individuals with high risk features. Data from the STOP trial demonstrated that the incidence of stroke was reduced by 90% in children with high risk TCDs when they were managed on a regular transfusion programme. In more recent years, the use of hydroxyurea as a disease modifying therapy has increasingly become our practice, particularly so since the publication of the BABY-HUG trial data in 2014. Hydroxyurea has significantly altered the clinical course of sickle cell disease in children and prior to this era, 11% of patients would experience a stroke before the age of 20 years. In light of the changing management strategies for children with sickle cell disease, we reviewed the past 10 years TCD results from our patients. Annual TCD evaluation of cerebral artery blood flow was performed by radiologists and radiographers accredited to the Kings College national training programme. Scans were performed using Philips iU22 scanners with dedicated F5-1 transducers as per the UK National Screening protocol. Velocities were measured in the middle (MCA), anterior (ACA) and posterior cerebral arteries (PCA), internal carotid artery (ICA) and bifurcation on right and left sides (10 measurements per scan). The TCD service at our centre has had a positive external peer review. Over the past 10 years, 303 TCD imaging scans have been performed on 53 children aged 2-18 years. The number of abnormal, high-risk results (cerebral blood flow velocity (CBF-V) >200 cm/s) has been zero. 137 scans were performed in children prior to those individuals commencing hydroxyurea therapy, and the results of 3 scans were conditional, based on an increased CBF-V (171–200 cm/s) detected in 1 or more arteries. The other 168 scans were performed on children who were receiving hydroxyurea, of which 4 results were conditional. 49 of the 53 children have continuously had a normal TCD with no conditional or abnormal results. 4 children developed transient conditional TCD. Abstract source

Sickle cell disease (SCD) is characterized by pain, typically, acute in onset with a subset of events which require hospitalization for treatment with opioid analgesics. A proportion of adults also experience nearly daily pain that appears to share features with chronic pain in other diseases. However, the prevalence of chronic SCD pain in adults is largely undefined. Furthermore, the relationship between chronic pain in SCD and mortality has not been evaluated despite the known association between frequent acute pain crises and increased risk of death. The American Pain Society Pain Taxonomy working group on SCD has recently proposed core diagnostic criteria for chronic pain, although these criteria were not based upon population based data. Results: Forty-nine (21%) met the chronic pain definition. Mean age was 31.1 versus 32.1 years, respectively, and there was no sex difference between groups. Characteristics distinguishing the chronic pain group from all others were a higher body mass index (BMI; P=0.007), more hospitalizations for SCD pain over the past year (mean 6.6 hospitalizations for the chronic pain group; P< 0.0001), a higher number of moderate pain days (i.e. missing work; mean of 66.3 days; P< 0.0001), avascular necrosis in 49% of chronic pain patients (odds ratio 2.53 compared to all others; 95% confidence interval 1.33 to 4.85; P=0.006) and a higher prevalence of any current opioid use (90% versus 69%, P=0.003). In men, priapism was more prevalent for those with chronic pain (71% versus 46% respectively; odds ratio 2.80; 95% confidence interval 1.07 to 7.34; P=0.04). Systolic and diastolic blood pressure were also higher with chronic pain, but these were not quite statistically significant (P=0.06 for both). Overall, the proportion of subjects with both chronic pain and any contributory disease complications defined by the Pain Taxonomy working group (like leg ulcers or avascular necrosis) was 57% (28 out of 49), even though leg ulcers by themselves were not associated with chronic pain (P=0.52). Direct bilirubin was also higher and approached significance (P=0.053), but no other lab studies were associated with chronic pain. Multivariable logistic regressions showed that the number of hospitalizations for pain during the 12 months prior to evaluation (P=2.14 x 10-6), current opioid use (P=0.02) and higher systolic blood pressure (P=0.007) were independent markers associated with chronic pain. Finally, the chronic pain group was not at increased risk of death (Hazard Ratio 1.26; 95% CI 0.24 - 6.63; P=0.79) in a Kaplan Meier survival analysis with a median follow-up of 1.4 years for 174 subjects. Abstract source

Sickle cell disease is a risk factor for stroke. Findings from previous studies examining an association between sickle trait and stroke have been conflicting (Roach ES, 2005; Caughey MC, et al, 2014).An estimated two million people in the United States (U.S.) carry sickle trait (Key NS, et al, 2015). Carrier prevalence among African American newborns is 7-8% and up to 4% among Caribbean Hispanics, especially among people from the Dominican Republic and certain other nationalities (Lorey FW, et al, 1996; Siddiqui S, et al, 2012). Trait carriers are at increased risk of renal papillary necrosis, chronic kidney disease and thrombosis (Naik RP, et al, Bucknor MD, et al, 2014; Porter B, et, 2014). We hypothesized that cohorts of high-risk elderly populations who carry sickle trait may provide an opportunity to examine the question of cerebrovascular risk within the context of other associated risk factors. Methods: We examined cross-sectional associations between sickle trait and MRI-defined cerebral infarct and small vessel abnormalities, defined by a quantitative trait of white matter hyperintensities (WMHs), in 1476 participants from two well-phenotyped, high-risk elderly population-based cohorts, the Washington Heights-Inwood Columbia Aging Project (WHICAP) (Brickman AM, et, 2008 and 2010) and the Northern Manhattan Study (NOMAS) (Monteith T, et al, 2014). Participants shared by the cohorts were eliminated from WHICAP data. All 536 African American and 940 Caribbean Hispanic participants in the combined cohorts were genotyped for sickle trait. MRI protocols and WMH phenotyping used in both cohorts were performed as previously described using a 1.5T scanner and common pathologically-informed algorithms with good intra-reader reliability (Brickman AM, 2008; Verhaaren BF, 2015; Gutierrez J, et al, 2015). Univariate and multivariable-adjusted analyses were performed with statistical software packages SAS, SPSS and R. Beta coefficients from the linear regression models (WMH as the outcome variable) were exponentiated for interpretation as odds ratios. Abstract source

Sickle cell disease (SCD) affects approximately 100,000 people in the United States (US) and accounts for 75,000 hospitalizations and $475 million in hospitalization costs per year. There is little information about which physician specialists provide the majority of outpatient care and their prescribing practices for SCD. Many suspect much of adult SCD outpatient care is provided by emergency medicine physicians because of lack of access to high quality care from hematologists and primary care. Here, we evaluate a facet of care in SCD by evaluating the outpatient medications frequently prescribed to SCD patients and the physician specialties most involved in writing those prescriptions. Methods: We used the National Disease and Therapeutic Index (NDTI), a nationally representative audit of outpatient visits in the continental US conducted by IMS Health. The survey includes approximately 4100 sampled physicians each calendar quarter who provide information about every clinical encounter during 2 consecutive workdays. Physicians are selected by random-stratified sampling by specialty and geographic region from the master lists of the American Medical Association and the American Osteopathic Association. The complex sampling frame allows extrapolation to national estimates for outpatient visits and associated prescriptions. Data for each visit include patient diagnoses based on codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and medications prescribed during these visits. The complex sampling frame allows extrapolation to national estimates for office visits and associated prescriptions. We analyzed medications prescribed for the years 2012 through 2015 for patients with SCD. Our analyses included all visits by patients with a recorded SCD diagnosis (International Classification of Diseases, Ninth Revision [ICD-9] codes 282.41–282.42, 282.60–282.64, 282.68, or 282.69). We used descriptive statistics to examine the counts of prescriptions. We aggregated quarterly data from 2012 to 2015 to present annual trends. With linear regression analysis, we assessed the rate of change of prescriptions each year. Abstract source

Despite the efficacy of Hydroxyurea (HU) in decreasing morbidity and mortality in adults with sickle cell disease (SCD) the uptake of and adherence with HU is poor, probably as the result of a combination of both physician and patient related factors. Lack of knowledge about HU, doubts regarding effectiveness, concerns over side effects and unrealistic expectations from HU treatment have been previously identified as barriers to the wider uptake of HU by the patient. Since approval of HU for SCD by the FDA in 1998, there has been a progressive increase of the use of HU in SCD. Changes in approach and practice over this time may have impacted the attitude towards HU of patients of different ages differently. The impact of patients’ age on the uptake and utilization of HU has not been studied. We investigated the impact of age on the attitudes of adult patients towards the purpose, side effects, associated risks and benefits of taking HU. Methods: We conducted qualitative interviews with adult SCD patients from a geographically diverse population recruited from national conferences and local SCD clinics. Data were gathered as part of a larger study of decision making regarding disease modifying therapies for SCD and development of a decision- aid tool for patients involving these disease-modifying therapies. We used a semi-structured open-ended interview guide to collect data. Audio recordings were transcribed verbatim. Transcripts were coded using qualitative content analysis with NVivo 11. We sought to understand attitudes of adult patients with SCD towards available treatment options. We then focused our analyses specifically on attitudes towards HU as a model for how SCD patients viewed their disease and treatment options. We also sought to interrogate differences in attitudes among patients who reached adulthood, before and after the general adoption of hydroxyurea as a treatment option for SCD. Results: Age of the 95 participants ranged from 18 years to 67 years old. Female = 71. While approximately 50% of all participants reported that they were currently taking HU, younger participants were more likely to be currently taking HU than the older participants (p = .05). Seventy percent of the younger adults (Age 18-30) reported they were currently taking HU as compared to 41% of the older adults (Age 31-67) [table 1]. Younger participants were more likely to report that the decision to accept a physician recommendation to start HU was made by their parent, though some participants decided to start HU as a young adult. Younger participants understood the purpose of HU as intended to improve “blood counts” thereby decreasing crises and hospital stays. They were hopeful that HU would help and thus focused on the potential for successfully managing SCD complications rather than on the side effects from HU. For those who decided to start as young adults, they offered positive accounts in regards to the decision to start HU and maintain the treatment. Abstract source

Hydroxyurea (HU) has been shown to be efficacious in individuals with sickle cell disease (SCD). Drug labeling gives prescribing guidance for use in adults, but use in children is based on expert consensus and not randomized trials. This leads to variation in HU initiation, counseling, monitoring, and discontinuation. Design/Method: We conducted an online survey of HU prescribing practices among providers in the New England Pediatric Sickle Cell Consortium caring for approximately 1000 children with SCD, from September-October 2013. Results: We had responses from 13 providers from 10 New England institutions. Six providers estimated that they had > 50% of eligible patients on HU. HU initiation indications used by >70% of respondents included: all patients with hemoglobin SS and SB0-thalassemia, conditional TCD velocities, >=3 pain episodes/year, multiple hospitalizations, and parental request. All providers felt HU was safe for children >2 years old, 7/11 offered it in children <2 years. Respondents reported that patient or family declining was the most common reason for not initiating HU; reasons given included the increased frequency of office visits, difficulty of daily medications, fear of side effects, concerns for dependency, and loss of fertility. Other reasons for ineligibility included hepatic or renal dysfunction, splenic sequestration, neutropenia, high baseline hemoglobin, and history of poor adherence. 90% of prescribers either provided or referred patients for counseling about birth control , 7/12 performed urine pregnancy tests routinely, and 33% of providers required documentation of birth control in females. Respondents typically started HU at 15-20 mg/kg/d, but maintenance doses varied widely, from 15 to 35mg/kg/d. Lab monitoring was done every 2-4 weeks during escalation, and every 2-3 months with stable dosing. Adherence was most commonly monitored by self-report and inferred by lab values. The top three indications to discontinue HU included missed visits, poor adherence or neutropenia. Abstract source

An estimated 93-98% of sickle cell disease (SCD) patients now reach adulthood in high resource countries. Studies show that this growing cohort of young adult SCD patients aged 18-26 years old experiences a marked rise in medical complications and early mortality, coinciding with decreased use of life-prolonging therapies and increased use of emergency care. Design/Method: 441 SCD patients transitioned from pediatric care at Texas Children’s Hematology Center (TCHC) between 01/1999 and 01/2014. We contacted these patients at their last known address and phone number to request completion of a 23 question survey assessing patient demographics, post-transition medical outcomes, and personal experiences. Results: 48 surveys were completed. 17 patients (35.4%) lack a provider, with top reasons being lack of insurance/funding (44%) and “can’t find a physician” (38%). Patients without an adult physician within 6 months of transition were less likely to have a physician currently (p<0.017). 83.3% of patients on hydroxyurea as pediatric patients (15/18) continued hydroxyurea therapy after transition. Subjects reported difficulties with finding knowledgeable adult providers, medical insurance, and inadequate transition preparation. Examples of qualitative results include comments such as the following: “The adult doctors are not aware of the disease…They have to call the pediatricians.” While another said, “[It was] hard finding a physician in the two years after TCHC [because of insurance loss]… my health worsened because I wasn’t getting the medication that I needed.” When asked, 94% of patients wanted a dedicated SCD transition clinic. 12 patients were identified as deceased from all causes. Abstract source

Under-5 mortality for children with sickle cell disease (SCD) in low and middle-income countries (LMIC) is high, with the majority of deaths likely related to infectious complications. In the United States, dramatic decreases in childhood mortality for SCD over the past 40 years have been aided by interventions to reduce mortality associated with infections. In LMIC, these interventions (i.e. penicillin prophylaxis, rapid investigation and treatment of febrile illness, and vaccination) may not be consistently available. Design/Method: A survey of English and French-speaking providers at SCD programs in LMIC. The survey was available online and offline, distributed via email distribution lists, at applicable meetings, and by referral. Results: Providers from 13 LMIC returned 27 interpretable surveys, including 23 from malaria-endemic areas. Newborn screening is associated with 34% (n=10/27) of programs. Pneumococcal conjugate vaccine is available at 66% (n=14/25) of programs. Penicillin prophylaxis is prescribed to some or all patients by 65% (n=17/26) of respondents. Malaria prophylaxis is prescribed by 83% (n=19/23) in malarial-endemic areas. Forty-eight percent of programs (n=14/27) have written fever management protocols. To patients with SCD presenting with fever, 21% (n=5/24) of respondents ‘always’ give antibiotics, although 54% (n=13/24) give antibiotics ‘almost always’. First line antibiotics are given orally by 27% (n=7/26); 77% (n=20/26) would consider oral antibiotics in some circumstances. The preferred first line antibiotic is ceftriaxone for 9/19 giving IV/IM antibiotics and amoxicillin-clavulanate for 4/7 giving oral antibiotics. At programs in malaria-endemic areas, 79% (n=18/23) ‘always’ or ‘almost always’ give antimalarials to febrile patients. Forty-six percent (n=12/26) of respondents report that a majority of febrile patients receive antibiotics prior to presentation. In malaria-endemic areas, 74% (n=17/23) report that a majority receive antimalarials prior to presentation. Abstract source