Looking ahead: ethical and social challenges of somatic gene therapy for sickle cell disease in Africa.

Somatic gene therapy will be one of the most exciting practices of genetic medicine in Africa and is primed to offer a "new life" for persons living with sickle cell disease (SCD). Recently, successful gene therapy trials for SCD in the USA have sparked a ray of hope within the SCD community in Africa. However, the high cost, estimated to exceed 1.5 million USD, continues to be a major concern for many stakeholders. While affordability is a key global health equity consideration, it is equally important to reflect on other ethical, legal and social issues (ELSIs) that may impact the responsible implementation of gene therapy for SCD in Africa. These include informed consent comprehension, risk of therapeutic misestimation and optimistic bias; priorities for SCD therapy trials; dearth of ethical and regulatory oversight for gene therapy in many African countries; identifying a favourable risk-benefit ratio; criteria for the selection of trial participants; decisional conflict in consent; standards of care; bounded justice; and genetic tourism. Given these ELSIs, we suggest that researchers, pharma, funders, global health agencies, ethics committees, science councils and SCD patient support/advocacy groups should work together to co-develop: (1) patient-centric governance for gene therapy in Africa, (2) public engagement and education materials, and (3) decision making toolkits for trial participants. It is also critical to establish harmonised ethical and regulatory frameworks for gene therapy in Africa, and for global health agencies to accelerate access to basic care for SCD in Africa, while simultaneously strengthening capacity for gene therapy.

Transitioning Adolescents With Sickle Cell Disease From Pediatric to Adult Care: Results From a New Survey of Health Care Professionals.

Transition from pediatric to adult care for adolescents and young adults (AYA) with sickle cell disease (SCD) comes at a time when a range of biopsychosocial issues occur simultaneously. A new survey sought information from physicians who treat AYA with SCD about their practices in how they transition pediatric patients to adult care. An online survey to physicians who treat SCD was conducted using SurveyMonkey between November 2019 and January 2020. Of 209 physicians who were contacted, 58 completed the survey; 62.1% treated primarily pediatric patients and 37.9% treated adults. Patient education on transition was regarded as "important" or "very important" by 94.2% of the physicians. Patients' knowledge about their disease and their ability to navigate the health care system were identified as 2 primary barriers to transition (mean 1.30 and 1.67 on a 3-point scale, respectively). Most physicians employ established models to facilitate the transition, including Got Transition (41.3%) and a biopsychosocial model (34.8%), with 34.8% using a mix of models and 23.9% not using an established model. Fewer than half (34.8%) rated their program as "very successful" or "successful." Transition protocols from pediatric to adult care should be re-examined to facilitate successful transition for AYA with SCD.

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model.

PURPOSE: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains. METHODS: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare. RESULTS: Higher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02-1.10, 95% CI range [1.004-1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58-3.28 95% CI range [1.18-4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46-0.64, 95% CI range [0.34-0.86]). CONCLUSIONS: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes.

Impact of Medicaid expansion on access and healthcare among individuals with sickle cell disease.

PURPOSE: Sickle cell disease (SCD) is associated with high acute healthcare utilization. The purpose of this study was to examine whether Medicaid expansion in California increased Medicaid enrollment, increased hydroxyurea prescriptions filled, and decreased acute healthcare utilization in SCD. METHODS: Individuals with SCD (≤65 years and enrolled in Medicaid for ≥6 total calendar months any year between 2011 and 2016) were identified in a multisource database maintained by the California Sickle Cell Data Collection Program. We describe trends and changes in Medicaid enrollment, hydroxyurea prescriptions filled, and emergency department (ED) visits and hospital admissions before (2011-2013) and after (2014-2016) Medicaid expansion in California. RESULTS: The cohort included 3635 individuals. Enrollment was highest in 2014 and lowest in 2016 with a 2.8% annual decease postexpansion. Although <20% of the cohort had a hydroxyurea prescription filled, the percentage increased by 5.2% annually after 2014. The ED visit rate was highest in 2014 and decreased slightly in 2016, decreasing by 1.1% annually postexpansion. Hospital admission rates were similar during the pre- and postexpansion periods. Young adults and adults had higher ED and hospital admission rates than children and adolescents. CONCLUSIONS: Medicaid expansion does not appear to have improved enrollment or acute healthcare utilization among individuals with SCD in California. Future studies should explore whether individuals with SCD transitioned to other insurance plans or became uninsured postexpansion, the underlying reasons for low hydroxyurea utilization, and the lack of effect on hospital admissions despite a modest effect on ED visits.

Lessons Learned from Building a Pediatric-to-Adult Sickle Cell Transition Program.

OBJECTIVE: More effective transitions and transfers of young people with sickle cell disease (SCD) into the adult healthcare setting is a focus of both primary care and specialty care medical organizations. Effective transition and transfer requires six core elements: establishing a policy, tracking progress, administering transition readiness assessments, planning for adult care, transferring to adult care, and integrating into an adult practice. We developed a program using these six core elements. The objective of our report was to assess the development and implementation of this program. METHODS: We used the six core elements to develop and implement a program at Virginia Commonwealth University for children and adolescents with SCD to transition to adult health care. RESULTS: We assessed individuals' differences by age and grade, their independent living skills, their feelings about moving to adult care; tallied and analyzed several assessment scales; and assessed transfer success and patient retention. CONCLUSIONS: The principles and lessons we learned in developing and implementing this program over 5 years, accompanied by caring, flexible, and dedicated care team members, often can overcome even severe barriers to care transitions.

Relation Between Religious Perspectives and Views on Sickle Cell Disease Research and Associated Public Health Interventions in Ghana.

Sickle cell disease (SCD) is highly prevalent in Africa with a significant public health burden for under-resourced countries. We employed qualitative research methods to understand the ethical, legal, and social implications of conducting genomic research in SCD under the Human Heredity and Health in Africa (H3Africa) initiative. The present study focused on religious and cultural aspects of SCD with the view to identifying beliefs and attitudes relevant to public health interventions in Ghana. Thematic analyses from individual and group interviews revealed six key areas of importance, namely, reliance on a supreme being; religion as a disruptive influence on health behaviors; role of religious leaders in information sharing and decision-making; social, religious, and customary norms; health and religious/supernatural beliefs; and need for social education and support through church and community. Findings suggest that public health programs in Ghana should not only aim at increasing knowledge and awareness about SCD and its management but also create an understanding of the relevance of genomics and alternative technological advancement to diagnosis and ethical decision-making around available options for health seeking. Future research should engage communities to help address the ethical and social implications of a persuasive religious influence on SCD-related health decisions.

Emergency department utilization by Californians with sickle cell disease, 2005-2014.

BACKGROUND: Clinical care for children and adults living with sickle cell disease (SCD) is often provided in the emergency department (ED). Population-based surveillance data can be used to describe the ED utilization patterns of this patient population. PROCEDURE: A cohort of pediatric and adult California patients with SCD was identified from multiple data sources, and 10 years (2005-2014) of their treat-and-release ED utilization data were analyzed. RESULTS: Among a cohort of 4,636 patients with SCD, 4,100 (88%) had one or more treat-and-release ED visits. There were 2.1 mean annual visits per person for the cohort (median 0.7; range 0-185). In a single year (2005), 53% had 0 treat-and-release ED visits, 35% had 1-3 visits, 9% had 4-10 visits, and 3% had 11 or more visits; this highest utilization group accounted for 45% of all patients' ED visits. ED utilization in this cohort was highest among young adults and also higher among older adults than pediatric patients. CONCLUSION: The majority of identified patients in each of the 10 years did not go to the ED, but nearly all had one or more such visits over the full span of time. This study highlights the power and utility of a multisource longitudinal data collection effort for SCD. Further study of the segment of the population with highest ED utilization may highlight areas where changes in healthcare and health policy could improve and extend the lives of patients with SCD.

Sensitivity of alternative measures of functioning and wellbeing for adults with sickle cell disease: comparison of PROMIS® to ASCQ-Me℠.

BACKGROUND: Sickle Cell Disease (SCD) causes profound suffering and decrements in daily functioning. Demand is growing for valid and reliable measures to systematically document these effects, particularly in adults. The Adult Sickle Cell Quality of Life Measurement System, ASCQ-Me℠, was developed for this purpose. ASCQ-Me℠ is one of four measurement systems housed within the Person-Centered Assessment Resource (PCAR), funded by the National Institutes of Health, to support clinical research. To help users select the best of these measures for adults with SCD, we evaluated and compared two PCAR systems: one designed to be "universally applicable" (the Patient-Reported Outcome Measurement Information System, PROMIS®) and one designed specifically for SCD (ASCQ-Me℠). METHODS: Respondents to PROMIS and ASCQ-Me questions were 490 adults with SCD from seven geographically-disbursed clinics within the US. Data were collected for six ASCQ-Me measures (Emotional Impact, Sleep Impact, Social Impact, Stiffness Impact, Pain Impact, SCD Pain Episode Frequency and Severity) and ten PROMIS measures (Pain Impact, Pain Behavior, Physical Functioning, Anxiety, Depression, Fatigue, Satisfaction with Discretionary Social Activities, Satisfaction with Social Roles, Sleep Disturbance, and Sleep-Related Impairment). Statistical analyses, including analysis of variance and multiple linear regression, were conducted to determine the sensitivity of measures to SCD severity. SCD severity was assessed via a checklist of associated treatments and conditions. RESULTS: For those with the most severe SCD, PROMIS scores showed worse health compared to the general population for nine of ten health domains: the magnitude of the difference ranged 0.5 to 1.1 standard deviation units. The PROMIS domains most severely affected were Physical Functioning and Pain (Impact and Behavior). Significant differences by tertile of the SCD-MHC were shown for most PROMIS short forms and all ASCQ-Me short and fixed forms. In most models, ASCQ-Me measures explained statistically significant unique variance in SCD-MHC scores complementary to that explained by corresponding PROMIS measures. CONCLUSIONS: Study results supported the validity of both PROMIS and ASCQ-Me measures for use in adults with SCD. Compared to comparable PROMIS scores, most ASCQ-Me scores were better predictors of SCD disease severity, as measured by a medical history checklist. The clinical implications of these results require further investigation.

Long-Term Pulmonary Function and Quality of Life in Children After Acute Respiratory Distress Syndrome: A Feasibility Investigation.

OBJECTIVES: To determine the feasibility of pulmonary function and quality of life evaluations in children after acute respiratory distress syndrome. DESIGN: A prospective follow-up feasibility study. SETTING: A tertiary PICU. PATIENTS: Children less than 18 years old with acute respiratory distress syndrome admitted between 2000 and 2005. INTERVENTION: Pulmonary function testing and patient and parental quality of life surveys approximately 12-month after acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: One hundred eighty patients met acute respiratory distress syndrome criteria; 37 (20%) died, 90 (51%) declined participation, 28 (16%) consented but did not return, and 24 (13%) returned for follow-up visit. Twenty-three patients completed quality of life testing and 17 completed pulmonary functions. Clinical characteristics of those who returned were no different from those who did not except for age (median age, 4.9 vs 1.8 yr). One-third had mild to moderate pulmonary function deficits. Quality of life scores were marginal with general health perception, physical functioning, and behavior being areas of concern. These scores were lower than scores in children with chronic asthma. Parental quality of life assessments report lower scores in single-parent homes but no differences were noted by race or parental employment status. CONCLUSIONS: Valuable information may be discerned from acute respiratory distress syndrome patients who return for follow-up evaluation. In this pilot study, up to one-third of children with acute respiratory distress syndrome exhibit pulmonary function deficits and 12-month postillness quality of life scores are lower than in children with chronic asthma. Parental perceptions of postillness quality of life may be negatively impacted by socioeconomic constraints. Long-term follow of children with acute respiratory distress syndrome is feasible and bears further investigation.

Using formative research to develop a counselor training program for newborn screening in Ghana.

Sickle cell disease (SCD), sickle cell trait (SCT) and related conditions are highly prevalent in sub-Saharan Africa. Despite the public health implications, there is limited understanding of the unique needs regarding establishing and implementing extensive screening for newborns and appropriate family counseling. We sought to gain understanding of community attitudes and beliefs about SCD/SCT from counselors and potential counselors in Ghana; obtain their input about goals for counseling following newborn screening; and obtain guidance about developing effective counselor education. Five focus groups with 32 health care providers and health educators from 9 of 10 regions in Ghana were conducted by trained facilitators according to a structured protocol. Qualitative data were coded and categorized to reflect common themes. Saturation was achieved in themes related to genetics/inheritance; common complications of SCD; potential for stigmatization; marital strain; and emotional stress. Misconceptions about SCT as a form of SCD were prevalent as were cultural and spiritual beliefs about the causes of SCD/SCT. Potential positive aspects included affected children's academic achievement as compensation for physical limitations, and family cohesion. This data informed recommendations for content and structure of a counselor training program that was provided to the Ministry of Health in Ghana.

Teaching About Genetics and Sickle Cell Disease In Fifth Grade.

ACKNOWLEDGMENTS: We are grateful to Laura McVittie Gray for her work on the development of the student activities described in this article. This work was made possible by a Science Education Partnership Award (SEPA), Grant Number R25RR020449, from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Additional support for this SEPA-funded project was provided by Grant Number UL1RR024131-01 from NCRR. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. ABSTRACT: A 5-lesson, 5th-grade instructional unit, "Genetics and Sickle Cell Disease," was developed and tested as part of a 40-lesson curriculum entitled SEEK (Science Exploration, Excitement, and Knowledge): A Curriculum in Health and Biomedical Science for Diverse 4th and 5th Grade Students. The genetics lessons include hands-on activities (e.g., DNA extraction from cheek cells), a simulated plant genetics experiment, and a classroom visit by a person with sickle cell disease, as well as by a health care practitioner who works with sickle cell patients or a scientist specializing in genetics. The unit was tested with 82 5th-grade students at public elementary schools in Oakland, CA; 96% were racial and ethnic minorities. The comparison group consisted of 84 5th-grade Oakland students racially/ ethnically, academically, and socio-economically matched to those in the experimental group. Both groups completed a 20-question, multiple-choice pre/posttest covering science concepts, scientific process, lifestyle choices, and careers. The experimental group showed significant improvement on 13 of 20 questions (P<.05, t-tests) and on the test as a whole, whereas the comparison group did not show significant improvement either on any of the questions or on the test as a whole. The experimental group improved on 10 concept questions, 2 scientific process questions, and 1 lifestyle question. Teachers rated the educational value of the unit as 9.5 on a scale from 1 (low) to 10 (high). These results show that genetics and sickle cell disease can be taught successfully in 5th grade, although they are not typically covered at this level.

Patient reports of health outcome for adults living with sickle cell disease: development and testing of the ASCQ-Me item banks.

BACKGROUND: Providers and patients have called for improved understanding of the health care requirements of adults with sickle cell disease (SCD) and have identified the need for a systematic, reliable and valid method to document the patient-reported outcomes (PRO) of adult SCD care. To address this need, the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) was designed to complement the Patient Reported Outcome Measurement Information System (PROMIS®). Here we describe methods and results of the psychometric evaluation of ASCQ-Me item banks (IBs). METHODS: At seven geographically-disbursed clinics within the US, 556 patients responded to questions generated to assess cognitive, emotional, physical and social impacts of SCD. We evaluated the construct validity of the hypothesized domains using exploratory factor analysis (EFA), parallel analysis (PA), and bi-factor analysis (Item Response Theory Graded Response Model, IRT-GRM). We used IRT-GRM and the Wald method to identify bias in responses across gender and age. We used IRT and Cronbach's alpha coefficient to evaluate the reliability of the IBs and then tested the ability of summary scores based on IRT calibrations to discriminate among tertiles of respondents defined by SCD severity. RESULTS: Of the original 140 questions tested, we eliminated 48 that either did not form clean factors or provided biased measurement across subgroups defined by age and gender. Via EFA and PA, we identified three subfactors within physical impact: sleep, pain and stiffness impacts. Analysis of the resulting six item sets (sleep, pain, stiffness, cognitive, emotional and social impacts of SCD) supported their essential unidimensionality. With the exception of the cognitive impact IB, these item sets also were highly reliable across a broad range of values and highly significantly related to SCD disease severity. CONCLUSION: ASCQ-Me pain, sleep, stiffness, emotional and social SCD impact IBs demonstrated exceptional measurement properties using modern and classical psychometric methods of evaluation. Further development of the cognitive impact IB is required to improve its sensitivity to differences in SCD disease severity. Future research will evaluate the sensitivity of the ASCQ-Me IBs to change in SCD disease severity over time due to health interventions.

A Quality Improvement Initiative to Improve Emergency Department Care for Pediatric Patients with Sickle Cell Disease.

OBJECTIVE: To determine whether a quality improvement (QI) initiative would result in more timely assessment and treatment of acute sickle cell-related pain for pediatric patients with sickle cell disease (SCD) treated in the emergency department (ED). METHODS: We created and implemented a protocol for SCD pain management in the ED with the goals of improving (1) mean time from triage to first analgesic dose; (2) percentage of patients that received their first analgesic dose within 30 minutes of triage, and (3) percentage of patients who had pain assessment performed within 30 minutes of triage and who were re-assessed within 30 minutes after the first analgesic dose. RESULTS: Significant improvements were achieved between baseline (55 patient visits) and post order set implementation (165 visits) in time from triage to administration of first analgesic (decreased from 89.9 ± 50.5 to 35.2 ± 22.8 minutes, P < 0.001); percentage of patient visits receiving pain medications within 30 minutes of triage (from 7% to 53%, P < 0.001); percentage of patient visits assessed within 30 minutes of triage (from 64% to 99.4%, P < 0.001); and percentage of patient visits re-assessed within 30 minutes of initial analgesic (from 54% to 86%, P < 0.001). CONCLUSIONS: Implementation of a QI initiative in the ED led to expeditious care for pediatric patients with SCD presenting with pain. A QI framework provided us with unique challenges but also invaluable lessons as we address our objective of decreasing the quality gap in SCD medical care.

Perceptions and preferences for genetic testing for sickle cell disease or trait: a qualitative study in Cameroon, Ghana and Tanzania.

Sickle cell disease (SCD) is a single gene blood disorder characterised by frequent episodes of pain, chronic anaemic, acute chest syndrome, severe disease complications and lifelong debilitating multi-system organ damage. Genetic testing and screening programs for SCD and the sickle cell trait (SCT) are valuable for early diagnosis and management of children living with SCD, and in the identification of carriers of SCT. People with SCT are for the most part asymptomatic and mainly identified as through genetic testing or when they have a child with SCD. This qualitative study explored perceptions towards genetic testing for SCD and SCT in Cameroon, Ghana, and Tanzania. The results show a general preference for newborn screening for SCD over prenatal and premarital/preconception testing, primarily due to its simpler decision-making process and lower risk for stigmatization. Premarital testing for SCT was perceived to be of low public health value, as couples are unlikely to alter their marriage plans despite being aware of their risk of having a child with SCD. Adolescents were identified as a more suitable population for SCT testing. In the case of prenatal testing, major concerns were centred on cultural, religious, and personal values on pregnancy termination. The study revealed a gender dimension to SCD/SCT testing. Participants mentionned that women bear a heightened burden of decision making in SCD/SCT testing, face a higher risk of rejection by potential in-laws/partners if the carriers of SCT, as well as the possibility of  divorce if they have a child with SCD. The study highlights the complex cultural, ethical, religious and social dynamics surrounding genetic testing for SCD and emphasises the need for public education on SCD and the necessity of incorporating genetic and psychosocial counselling into SCD/SCT testing programs.

A biopsychosocial-spiritual model of chronic pain in adults with sickle cell disease.

Chronic pain in adults with sickle cell disease (SCD) is a complex multidimensional experience that includes biologic, psychologic, sociologic, and spiritual factors. To date, three models of pain associated with SCD (i.e., biomedical model, biopsychosocial model for SCD pain, and Health Beliefs Model) have been published. The biopsychosocial multidimensional approach to chronic pain developed by Turk and Gatchel is a widely used model of chronic pain. However, this model has not been applied to chronic pain associated with SCD. In addition, a spiritual/religious dimension is not included in this model. Because spirituality/religion is central to persons affected by SCD, that dimension needs to be added to any model of chronic pain in adults with SCD. In fact, data from one study suggest that spirituality/religiosity is associated with decreased pain intensity in adults with chronic pain from SCD. A biopsychosocial-spiritual model is proposed for adults with chronic pain from SCD, because it embraces the whole person. This model includes the biologic, psychologic, sociologic, and spiritual factors relevant to adults with SCD based on past and current research. The purpose of this paper is to describe an adaptation of Turk and Gatchel's model of chronic pain for adults with SCD and to summarize research findings that support each component of the revised model (i.e., biologic, psychologic, sociologic, spiritual). The paper concludes with a discussion of implications for the use of this model in research.

Quality of Life in Sickle Cell Disease: What Matters.

Health-related quality of life (HRQoL) represents the practical effects of an illness in terms of symptoms and impacts, and of consequent treatments, as perceived by the patient. HRQoL is a complex multidimensional phenomenon in sickle cell disease (SCD) involving external stressors, thought patterns, emotional distress, physiological arousal, pain, and other complications of SCD. Social determinants of health comprise food and housing security, employment and education, and experiences of racism and discrimination; these social determinants also potentially affect health, HRQoL, and access to health care. Interventions must be implemented in partnership between individuals with SCD and their health-care providers.

Barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families: Report from a U.S. regional collaborative.

Sickle cell disease (SCD) is an inherited blood disorder that affects about 100,000 people in the U.S., primarily Blacks/African-Americans. A multitude of complications negatively impacts quality of life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD, but is underutilized. Negative and uninformed perceptions of hydroxyurea and barriers to its use hinder adherence and promotion of the medication. As the largest real-world study to date that assessed hydroxyurea use for children and adults with SCD, we gathered and analyzed perspectives of providers, individuals with SCD, and families. Participants provided information about socio-demographics, hospital and emergency admissions for pain, number of severe pain episodes interfering with daily activities, medication adherence, and barriers to hydroxyurea. Providers reported on indications for hydroxyurea, reasons not prescribed, and current laboratory values. We found that hydroxyurea use was reported in over half of eligible patients from this large geographic region in the U.S., representing a range of sickle cell specialty clinical settings and practices. Provider and patient/caregiver reports about hydroxyurea use were consistent with one another; adults 26 years and older were least likely to be on hydroxyurea; and the likelihood of being on hydroxyurea decreased with one or more barriers. Using the intentional and unintentional medication nonadherence framework, we found that, even for patients on hydroxyurea, challenges to taking the medicine at the right time and forgetting were crucial unintentional barriers to adherence. Intentional barriers such as worry about side effects and "tried and it did not work" were important barriers for young adults and adults. For providers, diagnoses other than HgbSS or HgbS-ß0 thalassemia were associated with lower odds of prescribing, consistent with evidence-based guidelines. Our results support strengthening provider understanding and confidence in implementing existing SCD guidelines, and the importance of shared decision making. Our findings can assist providers in understanding choices and decisions of families; guide individualized clinical discussions regarding hydroxyurea therapy; and help with developing tailored interventions to address barriers. Addressing barriers to hydroxyurea use can inform strategies to minimize similar barriers in the use of emerging and combination therapies for SCD.

Autonomic nervous system reactivity: children with and without sickle cell disease.

BACKGROUND: Previous studies of healthy children have indicated a link between autonomic nervous system (ANS) reactivity and health outcomes, but there is limited research on whether ANS reactivity is similar for children with chronic conditions. OBJECTIVE: The aim of this study was to determine if ANS reactivity differs for children with sickle cell disease (SCD) compared with a community sample of children without SCD. METHOD: In two cross-sectional, descriptive studies, 32 public school children without chronic health problems were compared with 33 children with SCD. The children were 5-8 years old and they completed standardized protocols measuring ANS responses (respiratory sinus arrhythmia and preejection period) during rest and challenge conditions in social, cognitive, sensory, and emotion domains. Reactivity was calculated as the difference between challenge response minus rest for each domain and overall. RESULTS: There were differences in the distributions of the samples in parent education and child age, so these variables were adjusted for in subsequent analyses. The community sample showed parasympathetic withdrawal (low respiratory sinus arrhythmia scores) and greater parasympathetic reactivity (low respiratory sinus arrhythmia difference scores and percentage of negative scores) compared with the children with SCD in the social (p < .05) and sensory (p < .05) domains. The children with SCD showed greater sympathetic reactivity (low preejection period difference scores) compared with the community children in the cognitive domain (p < .05), and a greater percentage of children with SCD versus the community children showed negative preejection period difference scores (sympathetic reactivity) in the social domain (p < .05). The community sample, but not the children with SCD, showed changes in respiratory sinus arrhythmia across domains (p < .05). DISCUSSION: Children with SCD may display a different pattern of ANS responses to laboratory challenges compared with children without SCD from the same community.

Improving Preventive Care for Children With Sickle Cell Anemia: A Quality Improvement Initiative.

Sickle cell disease is a complex chronic disorder associated with increased morbidity and early mortality. The Pediatric Quality Measures Program has developed new sickle cell-specific quality measures focused on hydroxyurea (HU) counseling and annual transcranial Doppler (TCD) screening; however, these measures have not been used in a clinical setting to inform quality improvement (QI) efforts. METHODS: From 2017 to 2018, 9 sickle cell subspecialty clinics from the Pacific Sickle Cell Regional Collaborative conducted a year-long QI collaborative focused on improving the percentage of patients with HU counseling and TCD screening based on the new quality measures. After an initial kick-off meeting, the 9 sites participated in monthly conference calls. We used run charts annotated with plan-do-study-act cycle activities to track each site's monthly progress and the overall mean percentage for the entire collaborative. RESULTS: There was an overall improvement in the aggregate HU counseling from 85% to 98% (P < 0.01). For TCD screening, referral frequency changed from 85% to 90% (P = 0.76). For both measures, the variation in frequencies decreased over the year. CONCLUSION: Over 1 year, we found that a regional QI collaborative increased HU counseling. Although referral for TCD screening increased, there was no overall change in TCD completion. Overall, this QI report's findings can help clinicians adopt and implement these quality measures to improve outcomes in children.