Barriers to Pediatric Sickle Cell Disease Guideline Recommendations.

National guidelines recommend that providers counsel all patients with sickle cell anemia about hydroxyurea (HU) therapy and screen children with sickle cell anemia annually for the risk of stroke with transcranial Doppler (TCD). We surveyed a national convenience sample of sickle cell disease clinicians to assess factors associated with low adherence. Adherence was 46% for TCD screening. Low adherence was associated with a lack of outcome expectancy (eg, a belief that there would be poor patient follow-up to TCD testing; P < .05). Adherence was 72% for HU counseling. Practice barriers (eg, lack of support staff or time) and a lack of agreement with HU recommendations were associated with low adherence (P < .05). This study demonstrates that different types of strategies are needed to improve TCD screening (to address follow-up and access to testing) versus HU counseling (to address physician agreement and practice barriers)

Social and Psychological Factors Associated with Health Care Transition for Young Adults Living with Sickle Cell Disease

Introduction: Due to advances in disease management, mortality rates in children with sickle cell disease (SCD) have decreased. However, mortality rates for young adults (YA) increased, and understanding of social and psychological factors is critical. The aim of this study was to explore factors associated with health care transition experiences for YA with SCD. Method: This was a qualitative descriptive study. A 45-minute semistructured interview was conducted with 13 YA (M = 21.5 years, SD = 1.73). Results: Results suggest that social and psychological factors and self-management experiences influence health care transition. Eight themes emerged: “need for accessible support”; “early assistance with goal setting”; “incongruence among expectations, experiences, and preparation”; “spiritual distress”; “stigma”; “need for collaboration”; “appreciation for caring providers”; and “feeling isolated.” Discussion: Consideration of cultural contexts will guide nurses in supporting health care transition. Designing culturally relevant interventions that address unique needs for YA living with SCD is warranted

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc

Sickle Cell Disease and H3Africa: Enhancing Genomic Research on Cardiovascular Diseases in African Patients.

Sickle cell disease (SCD) has a high prevalence in sub-Saharan Africa. There are several cardiovascular phenotypes in SCD that contribute to its morbidity and mortality. SCD is characterised by marked clinical variability, with genetic factors playing key modulating roles. Studies in Tanzania and Cameroon have reported that singlenucleotide polymorphisms in BCL11A and HBS1L-MYB loci and co-inheritance of alpha-thalassaemia impact on foetal haemoglobin levels and clinical severity. The prevalence of overt stroke among SCD patients in Cameroon (6.7%) and Nigeria (8.7%) suggests a higher burden than in high-income countries. There is also some evidence of high burden of kidney disease and pulmonary hypertension in SCD; however, the burden and genetics of these cardiovascular conditions have seldom been investigated in Africa. Several H3Africa projects are focused on cardiovascular diseases and present major opportunities to build genome-based research on existing SCD platforms in Africa to transform the health outcomes of patients

Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study.

The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain

Perceptions of US adolescents and adults with sickle cell disease on their quality of care

Importance: Sickle cell disease (SCD) is the most common inherited red blood cell disorder in the United States, and previous studies have shown that individuals with SCD are affected by multiple health disparities, including stigmatization, inequities in funding, and worse health outcomes, which may preclude their ability to access quality health care. This needs assessment was performed as part of the Sickle Cell Disease Implementation Consortium (SCDIC) to assess barriers to care that may be faced by individuals with SCD. Objective: To assess the SCD-related medical care experience of adolescents and adults with SCD. Design, Setting, and Participants: This one-time survey study evaluated pain interference, quality of health care, and self-efficacy of 440 adults and adolescents (aged 15 to 50 years) with SCD of all genotypes and assessed how these variables were associated with their perceptions of outpatient and emergency department (ED) care. The surveys were administered once during office visits by trained study coordinators at 7 of 8 SCDIC sites in 2018. Results: The SCDIC sites did not report the number of individuals approached to participate in this study; thus, a response rate could not be calculated. In addition, respondents were not required to answer every question in the survey; thus, the response rate per question differed for each variable. Of 440 individuals with SCD, participants were primarily female (245 [55.7%]) and African American (428 [97.3%]) individuals, with a mean (SD) age of 27.8 (8.6) years. The majority of participants (306 of 435 [70.3%]) had hemoglobin SS or hemoglobin S β0-thalassemia. Most respondents (361 of 437 [82.6%]) reported access to nonacute (usual) SCD care, and the majority of respondents (382 of 413 [92.1%]) noted satisfaction with their usual care physician. Of 435 participants, 287 (66.0%) reported requiring an ED visit for acute pain in the previous year. Respondents were less pleased with their ED care than their usual care clinician, with approximately half (146 of 287 [50.9%]) being satisfied with or perceiving having adequate quality care in the ED. Participants also noted that when they experienced severe pain or clinician lack of empathy, this was associated with a negative quality of care. Age group was associated with ED satisfaction, with younger patients (\u3c19 vs 19-30 and 31-50 years) reporting better ED experiences. Conclusions and Relevance: These results suggested that a negative perception of care may be a barrier for patients seeking care. These findings underscore the necessity of implementation studies to improve access to quality care for this population, especially in the acute care setting

Association between Hospital Admissions and Healthcare Provider Communication for Individuals with Sickle Cell Disease

Objective: To test the hypothesis that caregivers’ or adult participants’ low ratings of provider communication are associated with more hospital admissions among adults and children with sickle cell disease (SCD), respectively. Secondarily, we determined whether there was an association between the caregivers’ or participants’ health literacy and rating of providers’ communication. Methods: Primary data were collected from participants through surveys between 2014 and 2016, across six sickle cell centers throughout the U.S. In this cross-sectional cohort study, 211 adults with SCD and 331 caregivers of children with SCD completed surveys evaluating provider communication using the Consumer Assessment of Healthcare Providers and Systems (CAHPS), healthcare utilization, health literacy, and other sociodemographic and behavioral variables. Analyses included descriptive statistics, bivariate analyses, and logistic regression. Results: Participants with better ratings of provider communication were less likely to be hospitalized (odds ratio (OR) = 0.54, 95% confidence interval (CI) = [0.35, 0.83]). Positive ratings of provider communication were associated with fewer readmissions for children (OR = 0.23, 95% CI = [0.09, 0.57]). Participants with better ratings of provider communication were less likely to rate their health literacy as lower (regression coefficient (B) = −0.28, 95% CI = [−0.46, −0.10]). Conclusions: Low ratings of provider communication were associated with more hospitalizations and readmissions in SCD, suggesting the need for interventions targeted at improving patient-provider communication which could decrease hospitalizations for this population

Identifying barriers to evidence-based care for sickle cell disease: Results from the Sickle Cell Disease Implementation Consortium cross-sectional survey of healthcare providers in the USA

OBJECTIVES: Sickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based guidelines assist providers in caring for individuals with SCD, but adoption of these guidelines by providers has not been optimal. The objective of this study was to identify barriers to treating individuals with SCD. METHODS: The SCD Implementation Consortium aimed to investigate the perception and level of comfort of providers regarding evidence-based care by surveying providers in the regions of six clinical centres across the USA, focusing on non-emergency care from the providers\u27 perspective. RESULTS: Respondents included 105 providers delivering clinical care for individuals with SCD. Areas of practice were most frequently paediatrics (24%) or haematology/SCD specialist (24%). The majority (77%) reported that they were comfortable managing acute pain episodes while 63% expressed comfort with managing chronic pain. Haematologists and SCD specialists showed higher comfort levels prescribing opioids (100% vs 67%, p=0.004) and managing care with hydroxyurea (90% vs 51%, p=0.005) compared with non-haematology providers. Approximately 33% of providers were unaware of the 2014 NHLBI guidelines. Nearly 63% of providers felt patients\u27 medical needs were addressed while only 22% felt their mental health needs were met. CONCLUSIONS: A substantial number of providers did not know about NHLBI\u27s SCD care guidelines. Barriers to providing care for patients with SCD were influenced by providers\u27 specialty, training and practice setting. Increasing provider knowledge could improve hydroxyurea utilisation, pain management and mental health support

Intentional and unintentional nonadherence to hydroxyurea among people with sickle cell disease: A qualitative study

Hydroxyurea is an efficacious treatment for sickle cell disease (SCD), but adoption is low among individuals with SCD. The objective of this study was to examine barriers to patients' adherence to hydroxyurea use regimens by using the intentional and unintentional medication nonadherence framework. We interviewed individuals with SCD age 15 to 49.9 years who were participants in the Sickle Cell Disease Implementation Consortium (SCDIC) Needs Assessment. The intentional and unintentional medication nonadherence framework explains barriers to using hydroxyurea and adds granularity to the understanding of medication adherence barriers unique to the SCD population. In total, 90 semi-structured interviews were completed across 5 of the 8 SCDIC sites. Among interviewed participants, 57.8% (n = 52) were currently taking hydroxyurea, 28.9% (n = 26) were former hydroxyurea users at the time of the interview, and 13.3% (n = 12) had never used hydroxyurea but were familiar with the medication. Using a constructivist grounded theory approach, we discovered important themes that contributed to nonadherence to hydroxyurea, which were categorized under unintentional (eg, Forgetfulness, External Influencers) and intentional (Negative Perceptions of Hydroxyurea, Aversion to Taking Any Medications) nonadherence types. Participants more frequently endorsed adherence barriers that fell into the unintentional nonadherence type (70%) vs intentional nonadherence type (30%). Results from this study will help SCD health care providers understand patient choices and decisions as being either unintentional or intentional, guide tailored clinical discussions regarding hydroxyurea therapy, and develop specific, more nuanced interventions to address nonadherence factors