Transcranial Doppler Screening Research Articles

Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa

Introduction: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. Methods: After formal training and certification, local personnel screened children 2–16 years old; those with conditional (170–199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. Results: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8–1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. Conclusion: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.

Primary Prevention of Stroke in Children With Sickle Cell Anemia in Nigeria: Protocol for a Mixed Methods Implementation Study in a Community Hospital.

BackgroundIn Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in Nigeria (1R01NS094041: SPRING), TCD screening was adopted as standard care at Barau Dikko Teaching Hospital in Kaduna. However, with just 70 radiologists and only 3 certified in TCD screening in the state, just 5.49% (1101/20,040) of eligible children with SCA were screened. Thus, there is a need to explore alternate implementation strategies to ensure children with SCA receive standard care TCD screening to decrease stroke incidence.ObjectiveThis protocol describes a study to create a stroke prevention program in a community hospital in Kaduna through task shifting TCD screening to nurses and training medical officers to initiate and monitor HU utilization for stroke prevention.MethodsThis study will be conducted at 2 sites (teaching hospital and community hospital) over a period of 3 years (November 2020 to November 2023), in 3 phases using both quasi-experimental and effectiveness-implementation study designs. In the needs assessment phase, focus groups and structured interviews will be conducted with health care providers and hospital administrators to identify barriers and facilitators to evidence-based stroke prevention practices. Results from the needs assessment will inform intervention strategies and a process plan to fit the needs of the community hospital. In the capacity building phase, nurses and medical officers at the community hospital will be trained on TCD screening and HU initiation and monitoring. In the implementation phase, children with SCA aged 2-16 years will be recruited into a nonrandomized single-arm prospective trial to determine the feasibility of initiating a task-shifted stroke prevention program by recording recruitment, retention, and adherence rates. The Reach and Effectiveness components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework will be used to evaluate implementation outcomes between the community and teaching hospitals.ResultsThe needs assessment phase of the study was completed in February 2021. Manuscript on findings is currently in preparation. Capacity building is ongoing with TCD training and sickle cell disease and stroke education sessions for nurses and doctors in the community hospital. Recruitment for the implementation trial is expected to commence in July 2022.ConclusionsThis study proposes a structured, theory-driven approach to create a stroke prevention program in a community hospital in Kaduna, Nigeria, to decrease stroke incidence among children with SCA. Results will provide preliminary data for a definitive randomized clinical trial in implementation science.International Registered Report Identifier (IRRID)PRR1-10.2196/37927

Clinical and Imaging Data-Based Model for Predicting Reversible Posterior Leukoencephalopathy Syndrome (RPLS) in Pregnant Women With Severe Preeclampsia or Eclampsia and Analysis of Perinatal Outcomes.

Objective This study aimed to investigate the risk factors of reversible posterior leukoencephalopathy syndrome (RPLS) in pregnant women with severe preeclampsia or eclampsia (SPE/E) based on a predicting model and to analyze the perinatal outcomes. Methods From January 2015 to March 2020, 78 pregnant women data diagnosed with severe preeclampsia or eclampsia with cranial magnetic resonance imaging (MRI) and transcranial Doppler (TCD) screening in Xiangyang No. 1 People's Hospital and Jiangsu Province Hospital of Chinese Medicine were analyzed retrospectively. They were divided into the RPLS group (n = 33) and non-RPLS group (n = 45) based on the MRI results. The general clinical data (blood pressure, BMI, symptoms, and so forth), laboratory examination, TCD results, and perinatal outcomes in the two groups were compared. The risk factors of severe preeclampsia or eclampsia complicated with RPLS were analyzed by multivariate logistic regression. The prediction model and decision curve (DCA) were established according to the clinical-imaging data. Results The univariate analysis showed that poor placental perfusion, hypertension emergency, use of two or more oral antihypertensive drugs, headache, white blood cell (WBC) count, platelet (PLT) count, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), uric acid (UA), serum albumin (ALB), average flow velocity, and resistance index of the posterior cerebral and basilar arteries were significantly different in the RPLS group compared with the non-RPLS group (all P < 0.05). The multivariate logistic regression analysis showed that hypertensive emergency, headache, WBC, PLT, ALT, and average flow velocity of the basilar artery (BAAFV) were the risk factors in the RPLS group. The aforementioned clinical-imaging data modeling (general data model, laboratory examination model, TCD model, and combined model) showed that the combined model predicted RPLS better. DCA also confirmed that the net benefit of the combined model was higher. In addition, the incidence of postpartum hemorrhage, stillbirth, and preterm infants was higher in the RPLS group than in the non-RPLS group (all P < 0.05). Conclusions More postpartum complications were detected in pregnant women with severe preeclampsia or eclampsia complicated with RPLS. Hypertensive emergency, headache, WBC, PLT, ALT, and BAAFV were the important risk factors for RPLS. The combined model had a better effect in predicting RPLS.

Trends in quality of care among children with sickle cell anemia.

For decades, it has been recommended that children with sickle cell anemia (SCA) receive antibiotic prophylaxis to prevent serious infections and undergo transcranial Doppler (TCD) screening to identify those at highest risk of overt stroke. We assessed recent temporal trends in antibiotic prophylaxis prescription fills and TCD screening among children with SCA using validated quality measures. Using validated claims-based definitions, we identified children with SCA who were enrolled in Michigan or New York State (NYS) Medicaid programs (2011-2018). Among recommended age groups, two outcomes were assessed yearly: (a) filling of ≥300days of antibiotics, and (b) receipt of greater than or equal to one TCD. The proportion of children with each outcome was calculated by state. Temporal trends in each preventive service were assessed using generalized linear models. A total of 1784 children were eligible for antibiotic prophylaxis (Michigan: 384; NYS: 1400), contributing 3322 person-years. Annual rates of filling ≥300days of antibiotics ranged from 16% to 22% and were similar by state. There was no change in rates of antibiotic filling over time in Michigan (p-value: .10), but there was a decrease in NYS (p-value: .02). A total of 3439 children with SCA were eligible for TCD screening (Michigan: 710; NYS: 2729), contributing 10,012 person-years. Annual rates of TCD screening ranged from 39% to 45%, were similar by state, and did not change over time (p-values >.05). Most children with SCA do not receive recommended antibiotic prophylaxis and/or TCD screening. New, sustainable, and coordinated interventions across preventive services are urgently needed.

Transcranial doppler screening in patients with sickle cell anemia in tertiary care hospital

Transcranial doppler screening in patients with sickle cell anemia in tertiary care hospital

Improving Completion Rates of Transcranial Doppler Ultrasounds in Children with Sickle Cell Disease Using Quality Improvement Efforts: In-Clinic Vs. Population-Based Assessments

Introduction:People living with sickle cell disease (SCD) are at risk for stroke due to progressive cerebral vasculopathy. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) study showed that transfusion therapy in patients with abnormal cerebral blood flow velocities measured by transcranial doppler (TCD) ultrasound significantly reduced the risk for stroke. Based on the STOP and STOP II studies, the National Heart, Lung and Blood Institute (NHLBI) and American Society of Hematology (ASH) recommend annual TCD screenings for children with HbSS and HbSb0 genotypes from age 2-16. Despite this recommendation, studies show that fewer than half of eligible children with SCD complete annual TCD screening. Recently, Cabana and Treadwell et al. (2020) found high TCD referral and completion rates in a multi-site quality improvement (QI) initiative (85% baseline) using chart review. Another feasible approach to tracking guideline adherence uses administrative claims data which are derived from diagnostic and billing codes from statewide claims. Claims data can be used to assess population estimates for a clinic or a state, for all eligible patients, including those who may not routinely access care. In this study, we use administrative claims to assess TCD completion rates in the same clinics participating in the aforementioned QI initiative. We hypothesized that, population level rates would be lower than those assessed via chart review and that QI strategies may not lead to sustained TCD completion rates.Methods:Between August 2017 to August 2018, a QI initiative within the Pacific Sickle Cell Regional Collaborative (PSCRC) was conducted to improve referral and completion rates of TCD screenings. Site leads participated in a monthly QI learning collaborative, implementing and reporting on Plan-Do-Study-Act (PDSA) cycles, with bimonthly chart review data collection. Medicaid administrative claims from the four states with participating clinics, from 2017, 2018 (to assess baseline and post-QI initiative performance) and 2019 (to assess sustainability), were used to assess rates of TCD completion in the eligible pediatric population, using the specifications of a previously validated quality measure by Reeves et al (2019). Annual TCD completion rates and changes in completion rates over time were assessed for each site and state.Results:Five sites from four states in the PSCRC were included in the analysis. There was large variability in the number of eligible patients in each clinic (13-75) and state (23-588). Based on administrative claims, TCD clinic-level completion rates at baseline ranged from 41.7% to 69.2% at individual clinics. After 12 months of QI participation, TCD completion rates improved at allsites (range 4.6% to 29.2%). The site with the largest change improved TCD completion rate from 41.7% to 70.8% (n=24). All but one site had a decrease in TCD completion rate after completing the QI initiative and in 2019, TCD completion rates were within 10% of baseline completion rates at all sites (range -8.2% to 8.3%). At the statewide level, one state had a sustained improvement in TCD completion (improvement from baseline: 8.8%). In three of the four states providing data, TCD completion rates decreased from baseline (range -0.7% to -12.6%).Discussion:In a regional collaborative, we found improvements in TCD completion in the setting of a QI initiative focused on TCD, which were not sustained in the year after. This suggests the need for a systems-level approach to improvement, leading to feasible sustainability when no longer the focus of a collaborative. In addition, our data show that, when using administrative claims, rates of TCD completion are lower than rates when using chart review data (41.7% to 69.2% vs. 85% by chart review noted in prior publication). Thus, while site-specific medical record review provides insight into the quality of care for patients seen in the clinic, administrative claims data allow for a global understanding of the quality of care for the clinic population at risk, including those who do not attend clinic regularly. This suggests additional potential focus for quality improvement initiatives, such as systems to optimize outreach to patients who may not routinely access care. This type of outreach may best be done by health plans, potentially in partnership with sickle cell specialists, and would be an important tool for improving health for children with SCD. DisclosuresVissa: Global Blood Therapeutics Inc: Research Funding. Treadwell: National Alliance of Sickle Cell Centers: Other: Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease.

Limited Access to Transcranial Doppler Screening and Stroke Prevention for Children with Sickle Cell Disease in Europe: Results of a Multinational Eurobloodnet Survey

Background:Children with sickle cell disease (SCD) are at increased risk of cerebrovascular events such as stroke, silent infarcts and neurocognitive impairment. The role of Transcranial Doppler ultrasound scanning (TCD) to identify sickle cell anemia (SCA) children at high risk of stroke is well established. Adam et al in 1998 recommended those with abnormal cerebrovascular flow velocities are offered prophylactic blood transfusion therapy to prevent stroke between ages 2 to 16 years. Therefore, TCD screening for stroke prevention in now is a mandatory in all guidelines for the management of children with SCA. However, there is still no uniform implementation of the program globally and in European countries (Rees 2016). Moreover, the information available on the quality of the TCD screening is limited to educational experiences in a few countries (Inusa 2019) but to evaluation of stroke prevention programs has been performed in Europe.As more disease modifying therapies become available for children with SCD, it is mandatory to know TCD availability, screening practices, and real-world data on stroke prevention in Europe.EuroBloodNet is the European Reference Network (ERN) on rare Hematological Disorders, one of the 24 ERN established by the European Union to improve care of patients with rare disorders in Europe. EuroBloodNet's main goal is to improve the healthcare and overall quality of life of patients with a Rare Hematological Disease by: 1) Improving equal access to highly specialized healthcare delivery through a multidisciplinary patient centered approach; 2) Enhancing the best practices in prevention, diagnosis and safe clinical care across Europe based on promotion of evidence based guidelines.We wanted to assess the state of the art of TCD screening and stroke prevention programs in European Expert Centers.Methods: An online survey was developed by SCD experts in 5 European countries and sent to all Representatives of the Health Care Providers (HCP) and the Red Cell Disorder representatives in each HCP within the EuroBloodNet network, as well as to National Representatives of Scientific Societies within European Countries. Items in the survey are listed in Table 1.Results81 hematologists or pediatricians from 77 centers in 16 European countries responded to the survey (14/16 in Western Europe); 39/77 (51%) were EuroBloodNet Expert centers, 14/77 (18%) were under evaluation as being recognized; 67/77 specified their expertise: 24% were pediatric, 3% adult, 58% both; 12 centers had >200 patients in the age range 1-16 years.36% Physicians reported not having a dedicated TCD/TCDi service for children with SCD so exams had to be performed by cardiologists (10%), general radiologists (28%), TCD is not performed (31%), or patients have to be sent in another center (31%). 74% reported requesting annual TCD for their patients, but to the question “What percentage of your patients receives annual TCD” only 28% confirmed that all their patients managed to actually receive annual TCD, due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%) (i.e TCD in another city), lack of funds for dedicated staff or equipment (11%), or other reasons.Only 74% of hematologists were aware of the protocol in use at their center by the staff performing TCD; the STOP criteria were applied by 64% of the physicians, mainly due non evaluation of the Internal Carotid Artery. The extracranial part of the carotid artery was evaluated only in 30% of the respondents.In case of abnormal/conditional TCD results, the approach varies and is not uniform across centers.ConclusionsOur data show that less than 30% of children with SCD followed in European Centers receive annual TCD according to recognized guidelines. This first multinational European survey allowed the identification of issues related to the lack of access to TCD, lack of trained staff, lack of adequate protocols for implementation of TCD and treatment afterwards, which will need to be addressed through dedicated actions. [Display omitted] DisclosuresCasale: Novartis Farma SpA: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mañú Pereira: Novartis: Research Funding; Agios Pharmaceuticals: Research Funding. de Montalembert: Vertex: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Colombatti: Global Blood Therapeutics: Research Funding; Addmedica: Consultancy; Forma Therapeutics: Consultancy; Novartis: Consultancy; NovoNordisk: Consultancy; BlueBirdBio: Consultancy; Global Blood Therapeutics: Consultancy; BlueBirdBio: Research Funding.

Study of transcranial Doppler ultrasound and endothelin-1 in children with sickle cell anemia: a single-center study

To assess the impact of our transcranial Doppler (TCD) screening program on the incidence of a first stroke in children with sickle cell anemia and to study the role of elevated serum endothelin-1 (an inflammatory mediator) in these children. Background: stroke is a major complication of sickle cell disease (SCD), even in very young children. About 11% of children with homozygous sickle cell anemia (SS) develop stroke by the end of the second decade of life. The underlying etiology in most cases is an ischemic stroke caused by large-vessel stenosis or occlusion. Transcranial Doppler (TCD) recommended as a routine screening test to identify children at high risk of developing a stroke, measures flow velocities within large intracranial arteries. TCD should be routinely performed in children between 2 and 16 years as this age group is at the highest risk of sickle cerebral vasculopathy. We carried out a prospective case-control study which included 2 groups: a patient group consisted of 30 children with sickle cell anemia and sickle thalassemia and a group of 30 healthy children of matched age and sex. Each group included 11 males (36.5%) and 19 females (63.5%); the age range was 2 to 17 years. Both groups underwent a thorough clinical examination and laboratory tests (CBC, liver and renal function, serum ferritin and endothelin-1). Additionally, TCD was performed in all children included in the patient group. According to the results of TCD, time-averaged mean of the maximum velocity (TAMMX) was &lt; 170 cm/s (normal), 170–200 cm/s (conditional), ≥ 200 cm/s (high risk) in 20 (66.7%), 4 (13.3%) 6 (20%) patients, respectively. The level of endothelin-1 was significantly higher in the patients (57.1 ± 91.3) than in the controls (21.9 ± 14.8). Hemoglobin concentration was significantly lower in the patient group than in the control group, but the levels of reticulocytes, WBCs and serum ferritin were significantly higher in the patients than in the healthy controls. Serum Endotheline-1 level was higher in patients with sickle cell anemia than control group.

Epidemiology of Stroke in Sickle Cell Disease.

Sickle cell disease is the most common cause of stroke in childhood, both ischaemic and haemorrhagic, and it also affects adults with the condition. Without any screening or preventative treatment, the incidence appears to fall within the range 0.5 to 0.9 per 100 patient years of observation. Newborn screening with Penicillin prophylaxis and vaccination leading to reduced bacterial infection may have reduced the incidence, alongside increasing hydroxyurea prescription. Transcranial Doppler screening and prophylactic chronic transfusion for at least an initial year has reduced the incidence of stroke by up to 10-fold in children with time averaged mean of the maximum velocity >200 cm/s. Hydroxyurea also appears to reduce the incidence of first stroke to a similar extent in the same group but the optimal dose remains controversial. The prevention of haemorrhagic stroke at all ages and ischaemic stroke in adults has not yet received the same degree of attention. Although there are fewer studies, silent cerebral infarction on magnetic resonance imaging (MRI), and other neurological conditions, including headache, epilepsy and cognitive dysfunction, are also more prevalent in sickle cell disease compared with age matched controls. Clinical, neuropsychological and quantitative MRI screening may prove useful for understanding epidemiology and aetiology.

Identified barriers and facilitators to stroke risk screening in children with sickle cell anemia: results from the DISPLACE consortium

BackgroundChildren with sickle cell anemia are at risk for stroke. Ischemic stroke risk can be identified among children ages 2–16 years with sickle cell anemia using transcranial Doppler ultrasound. Despite strong recommendations for transcranial Doppler screening in guidelines released by the National Heart, Lung, and Blood Institute, implementation of transcranial Doppler screening in sickle cell anemia remains suboptimal. The purpose of this study was to identify barriers and facilitators to transcranial Doppler screening in a large national consortium to inform subsequent implementation interventions.MethodsA qualitative descriptive approach was used to conduct 52 semi-structured interviews with a sample of patients with sickle cell anemia, their parents or primary caregivers, and healthcare providers dispersed across the United States. Interviews took place from September 2018 through March 2019. Directed content analysis was conducted with an adapted version of the Multilevel Ecological Model of Health as an initial coding framework, completed July 2019. Frequency analysis was conducted to determine predominant barrier and facilitator themes.ResultsFourteen barrier themes and 12 facilitator themes emerged representing all levels of the ecological framework. Two barrier themes (Logistical Difficulties and Competing Life Demands and Gaps in Scheduling and Coordination), and 5 facilitator themes (Coordination, Scheduling and Reminders; Education and Information; Provider and Staff Investment and Assistance; Positive Patient Experience; and Convenient Location) were predominant.ConclusionsBarriers and facilitators to transcranial Doppler screening in children with sickle cell anemia are complex and occur across multiple ecological levels. One barrier theme and 3 facilitator themes were found to be optimal to address in subsequent implementation interventions.

Implementation Of Transcranial Doppler Ultrasonography Screening and Primary Stroke Prevention In Urban and Rural Sickle Cell Disease Populations

Transcranial doppler (TCD) ultrasonography has been used successfully to identify children with sickle cell disease (SCD) at increased risk of stroke. A large randomized trial (STOP trial) demonstrated that initiation of chronic transfusions as primary stroke prevention in children with an abnormal TCD significantly reduced stroke risk. Based on these findings, annual TCD screening and primary stroke prevention for patients with abnormal findings are considered standard of care (SOC) for children with SCD. We report here results describing the implementation of TCD screening and primary stroke prevention in both urban and rural clinical practice.A retrospective chart review was conducted to identify children ages 2-16 years with Hgb SS or Sß0 thalassemia and no history of stroke. Patients are followed in the local urban comprehensive sickle cell program at Georgia Regents University of in 4 outreach clinics in rural Georgia. Starting in 2010 TCDs conducted by a STOP trained sonographer were offered three times annually in the rural clinics. All TCD results were recorded before and after the implementation of the rural TCD program. SOC is defined as having one TCD performed annually between January 1, 2010 and December 31,2012 starting at age 2 years in patients with no history of abnormal TCD.A total of 213 children were identified who met inclusion criteria. Table 1 describes demographic and TCD information since 2010. Prior to 2010 20% of patients had no history of TCD; following implementation of the rural TCD program 7% of patients never had a TCD (p≤ 0.01). The percentage of patients with conditional or normal TCD results since 2010 is comparable between urban and rural clinics, whereas the proportion of patients with abnormal TCDs is higher in the rural clinics (p=0.01). Overall 41% of patients achieved SOC screening. There was no difference in SOC rates between urban and rural clinics (Table 1, p=0.12). Furthermore, there was no difference in SOC rates in the urban and rural clinics in patients with a history of normal (33% and 42% respectively, p=0.21) or conditional TCDs (50% and 58% respectively, p=0.72). Among the group of patients with a history of abnormal TCDs (n=18) the majority of patients were on chronic transfusions (83%) and none have experienced a stroke. While rural patients were able to receive transfusions locally, monitoring of transfusions was difficult with 38% and 31% of rurally transfused patients lacking documentation of Hgb S% and ferritin levels respectively in the past year. [Display omitted] We report here data describing implementation of the STOP trial recommendations in clinical practice with unique data on rural patients. Our data demonstrates that rural TCD screening is feasible and can achieve SOC equal to that in an urban setting. We did find a higher number of abnormal TCDs in the rural population, perhaps secondary to differences in TCD sonographer training or an unrecognized disparity in care. While the majority of children (93%) have received at least one TCD, a significant number of patients are not obtaining annual SOC screening. Chart review indicated common barriers include adherence with clinic appointments, refusal of screening, and loss to follow up care. Unlike screening, implementation of primary stroke prevention in rural patients is difficult with minimal laboratory data being followed by the hematologist. In conclusion, our data suggest that practice and physician level barriers exist that impact the ability to provide SOC primary stroke prevention. Future research should target quality measures to improve practice level barriers, provide parental education on the importance of screening and novel interventions to enhance patient adherence. Disclosures:No relevant conflicts of interest to declare.

Testing the Use of Data Drawn from the Electronic Health Record to Compare Quality.

Introduction:Health systems spend $1.5 billion annually reporting data on quality, but efficacy and utility for benchmarking are limited due, in part, to limitations of data sources. Our objective was to implement and evaluate measures of pediatric quality for three conditions using electronic health record (EHR)-derived data.Methods:PCORnet networks standardized EHR-derived data to a common data model. In 13 health systems from 2 networks for 2015, we implemented the National Quality Forum measures: % children with sickle cell anemia who received a transcranial Doppler; % children on antipsychotics who had metabolic screening; and % pediatric acute otitis media with amoxicillin prescribed. Manual chart review assessed measure accuracy.Results:Only 39% (N = 2,923) of 7,278 children on antipsychotics received metabolic screening (range: 20%–54%). If the measure indicated screening was performed, the chart agreed 88% of the time [95% confidence interval (CI): 81%–94%]; if it indicated screening was not done, the chart agreed 86% (95% CI: 78%–93%). Only 69% (N = 793) of 1,144 children received transcranial Doppler screening (range across sites: 49%–88%). If the measure indicated screening was performed, the chart agreed 98% of the time (95% CI: 94%–100%); if it indicated screening was not performed, the chart agreed 89% (95% CI: 82%–95%). For acute otitis media, chart review identified many qualifying cases missed by the National Quality Forum measure, which excluded a common diagnostic code.Conclusions:Measures of healthcare quality developed using EHR-derived data were valid and identified wide variation among network sites. This data can facilitate the identification and spread of best practices.

Quality of Care in United States Children with Sickle Cell Anemia

Quality of Care in United States Children with Sickle Cell Anemia

Transcranial Doppler Screening in Children with Sickle Cell Disease, in Venezuela. A Collaborative Effort

▪Venezuela is part of the Caribbean region, where Sickle Cell Disease (SCD) is frequent, due to the slaves brought during the Spanish conquest of the Americas. Neurovascular disease and stroke, are debilitating and can be even fatal, when present in these children, as it is well known. Transcranial Doppler (TCD) is an important tool, for prevention and follow up of these patients, and is underutilized in the developing world, mainly due to cost.OBJECTIVEOrganizing an efficient TCD program, that can reach many children affected by SCD, in Venezuela.DESIGN/SETTINGWe organized a team to provide TCD screening to children with SCD, in a collaborative effort, led by hematologists (the authors of this study). Novartis pharmaceutical provided the TCD machine -portable EZ-Dop system, DWL. Patients were assessed at a single center (Hospital Dr Carlos Arvelo, Caracas), but were referred by other centers, during a 6 month period. TCD was performed by radiologists in training, and by attending hematologists, previously trained for this procedure, at an academic, third level hospital, from January to June, 2017.PATIENTSEighty eight (88) pediatric patients, aged 2 to 15, affected by SCD, either from the pilot institution or referred, were screened by TCD, at our center. Parents were required to sign an informed consent, after the procedure was explained to them. Diagnostic electrophoresis were reviewed, for entering the study. Other data were plotted, such as current treatment, laboratory values, as well as relevant clinical information.INTERVENTIONTCD exam, at right and left temporal sides, using the standard STOP study protocol. Middle Cerebral Artery (MCA) and Anterior Cerebral Artery (ACA) velocities were assessed. Technical support from international expertise, was sought for reassurance. Normal was defined as mean velocitiy below 170cm/s. Conditional between 170cm/s and less than 200cm/s. Abnormal was defined above 200cm/s. Patients were not charged for the intervention. Collaboration from colleague hematologists, who referred their patients, was achieved. Patients who were found to be abnormal, were either transfused at our center, during the following 24 hours, or were contacted with their primary physician, for prompt intervention. Education and advice was provided to patients, if requested, as per the clinician's criteria.MAIN OUTCOME MEASURETCD readings were reported in a standardize format, as Normal, Conditional or Abnormal, according to the median velocity measure, of the MCA and ACA. Recommendations and follow up was provided to the patients, on every case.RESULTSTen patients 10/88 (11%) had abnormal readings, and were treated with a transfusion or partial exchange transfusion, at our institution. Their primary caregiver was contacted. Eight patients 8/88 (9%) had conditional results, and were suggested to repeat at the following session, no longer than 2 weeks. Sixty two children 62/88 (79%) had normal readings, and were suggested to repeat in 1 year.CONCLUSIONSTCD screening is feasible, in a collaborative effort, as an important tool for prevention and follow up, in children affected by SCD, in the developing world. DisclosuresNo relevant conflicts of interest to declare.

Increased prevalence of Stroke Recurrence and Stroke Related Mortality in Children with Sickle Cell Disease in Nigeria: evidence for a Secondary Stroke Prevention Trial.

Introduction- Nigeria has the highest burden of sickle cell anemia (SCA) in the world accounting for 50% of the 300,000 SCA births globally. In a recent survey conducted locally in Nigeria, Kano state was shown to have the highest number of children with SCA in Nigeria, with Kano metropolitan city alone having over 15,000 children with SCA. Stroke is one of the most devastating yet preventable complications in children with SCA. Without transcranial Doppler (TCD) screening and treatment, approximately 7 to 10% of the children with SCA will develop strokes. Among untreated children with strokes, there is at least a 50% recurrence rate after 2 years. Due to the high rate of stroke recurrence and the absence of regular blood transfusion therapy as a viable option due to availability, poor parental acceptance of blood transfusion, and cost, hydroxyurea therapy is the only viable option for the majority of children. However, the benefit and risks of hydroxyurea for secondary stroke prevention is poorly defined in Nigeria.Methodology- In preparation for a phase III trial of hydroxyurea for secondary stroke prevention in children with SCA in sub-Saharan Africa, we initiated a standard care protocol in 2014 to manage children with strokes at Aminu Kano Teaching Hospital Kano, Nigeria, to determine the prevalence of stroke among children with SCA between Jan 2014 to May 2017. Ethical approval to conduct the study was received from the ethics committee of Aminu Kano Teaching hospital in Kano, Nigeria.Result-We identified 29 children with SCA who had an initial stroke within the study period, with 7 children having >1 stroke, and a mortality rate of 6.9% (2/29). Death was unrelated to any toxicity associated with hydroxyurea. None of the children treated with hydroxyurea, had therapy held because of myelosuppression or anemia. The rate of initial stroke in the pediatric clinic population of approximately 500 children (age birth through 12 years) over a three-year period was 1.97 per 100 patient-years. The median age for the first stroke was 5.6 years (range 1.1 to 14.2 years). Children with initial strokes were followed for a total of 38.8 years and had a rate of recurrence of 18.1 events per 100 patient-years, (figure 1) significantly below the expected rate of 29 events per 100 patient years if no treatment was offered, but a significantly higher incidence rate compared to regular blood transfusion of 1.9 events per patient year. Of the patients with an initial stroke, 65.5% received an exchange transfusion and 92.6% were either already on hydroxyurea (n=1) or started on fixed dose hydroxyurea (n=24), 20 mg/kg/day, within 2 months of the stroke, as part of standard care. The median modified Rankin was 1 with a range from 0 to 6, on the gross motor function classification system score. 10 children (40.0%) had normal function and 6 (24.0%) had level III or higher. Both measurements were completed at a median of 1.6 years (IQR 1.9 years) after the initial stroke. (Table I)Conclusion-Our results provide strong evidence for the high prevalence of stroke and death following a stroke in children with SCA in Nigeria. Optimal hydroxyurea dose for secondary stroke prevention is unknown in low-resource setting. Given the prevalence of strokes in unscreened and untreated children with SCA, primary and secondary stroke prevention program are a public urgency in children with SCA living in Nigeria. We are currently conducting a randomized controlled trial for secondary prevention of strokes comparing fixed dose of 20 mg/kg/day vs 10 mg/kg/day (NCT NCT01801423). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Transcranial Doppler Findings Among Gulf Arabs

▪Background: Transcranial Doppler (TCD) is used to identify patients with sickle cell disease (SCD) at risk for stroke. We have carried out TCD studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Southern Iraq and UAE) to document the prevalence of abnormal TCD findings.Methodology: The patients were recruited from outpatient clinics and studied in steady state. TCD was performed using standard equipment with experienced operators. Time-averaged mean of maximum velocity (TAMMV) was documented in the arteries of the Circle of Willis. The hemoglobin (Hb) genotype was confirmed and the fetal Hb (HbF) level and complete blood counts were determined.Results: There were 415 patients in the study, aged 2 to 18 years (mean of 8.6±3.5). None of the patients had abnormal TAMMV (i.e. >200 cm/sec), while only 13 (3.1%), all from Iraq had conditional values in the right middle cerebral artery (MCA) and 7 (1.7%) in the left MCA. There were no significant gender differences, and both the Hb genotype (SS, Sβ0thal or SD) and the use of hydroxyurea did not show consistent influence on TAMMV. Total hemoglobin, reticulocyte count, serum bilirubin and HbF showed varying degrees of association with TAMMV in the different vessels.Conclusions: This study has demonstrated the rarity of abnormal TCD findings among Peninsular Arab patients with SCD. This might be related to the haplotype, elevated HbF or may represent a racial variation. The guidelines for TCD screening in this population need further studies and recommendations. DisclosuresNo relevant conflicts of interest to declare.

Transcranial Doppler Screening in a Current Cohort of Children With Sickle Cell Anemia: Results From the DISPLACE Study.

Stroke prevention guidelines for sickle cell anemia (SCA) recommend transcranial Doppler (TCD) screening to identify children at stroke risk; however, TCD screening implementation remains poor. This report describes results from Part 1 of the 28-site DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study, a baseline assessment of TCD implementation rates. This report describes TCD implementation by consortium site characteristics; characteristics of TCDs completed; and TCD results based on age. The cohort included 5247 children with SCA, of whom 5116 were eligible for TCD implementation assessment for at least 1 study year. The majority of children were African American or Black, non-Hispanic and received Medicaid. Mean age at first recorded TCD was 5.9 and 10.5 years at study end. Observed TCD screening rates were unsatisfactory across geographic regions (mean 49.9%; range: 30.9% to 74.7%) independent of size, institution type, or previous stroke prevention trial participation. The abnormal TCD rate was 2.9%, with a median age of 6.3 years for first abnormal TCD result. Findings highlight real-world TCD screening practices and results from the largest SCA cohort to date. Data informed the part 3 implementation study for improving stroke screening and findings may inform clinical practice improvements.

Transcranial Doppler screening in Nigerian children with sickle cell disease: A 10-year longitudinal study on the SPPIBA cohort.

Primary stroke prevention programmes for children with sickle cell disease (SCD) have been shown to be feasible interventions in resource-poor countries. Different hydroxyurea (HU) regimens have been utilised in ameliorating the severity of SCD. To determine the long-term outcomes of the stroke prevention programme for children with SCD in Ibadan (SPPIBA), Nigeria. A longitudinal study of 396 children with haemoglobin SS disease who had been on the stroke prevention programme for a minimum period of 5years. All enrollees had nonimaging TCD performed at baseline and thereafter 3-monthly or annually. Children with TCD velocities ≥170cm/s were treated with HU by dose-escalation regimen. The mean age at first TCD examination was 102 ± 46.7months and the period of follow-up ranged from 5 to 10years (mean=7.2 ± 1.7). Time to significant decline in TCD velocities ranged from 5 to 35months, (median=10.0months). The minimum dose of HU required to achieve significant decline in TCD velocities ranged from 15 to 31mg/kg/day, mean 23.7 (±3.9). HU dose escalation beyond 20mg/kg/day was required to attain significant reductions in the time-averaged mean of maximal velocities (TAMMV) in 69.1% of the cases. Two stroke events occurred giving a stroke incidence of 0.08 per 100 patient-years. The majority of Nigerian children with SCD and elevated TCD velocities achieved significant decline in TAMMV within the first year of HU therapy but on higher doses of HU. It might be important to individualise HU doses for optimal outcomes in primary stroke prevention.

Transcranial Doppler Screening In Children with Sickle Cell Disease of South Gujarat Population

Background: TCD (Transcranial Doppler) is a well-established study to predict Cerebrovascular stroke in SCD (Sickle cell disease). We aim to establish baseline TCD findings in Indian children with SCD and compare the results with the available STOP (Stroke prevention trial in Sickle Cell Anemia) protocol. We would also compare TCD findings in homozygous sickle cell disease and heterozygous sickle cell trait.&#x0D; Material and Methods: Seventy nine children with SCD were included in this study for one year period. TCD was performed and TAMMV (time-averaged maximum mean) velocity in the middle cerebral, anterior cerebral, posterior cerebral and internal carotid arteries was measured. Children were divided into two groups. Group I (56 homozygos–70.88%) and group II (23 heterozygos–29.11%).&#x0D; Results: In group I, 50 children fall in normal range with average TAMM velocity of 127.59 ± 17.48 cm/s. There was 1 (1.78%) abnormal result and 5 (8.9%) conditional results in group I. All results were normal in group II with average TAMM velocity of 116.33 ± 12.412 cm/sec. Middle cerebral artery was the only affected vessels amongst all.&#x0D; Conclusions: In our study, there was low prevalence of abnormal TCD results as compared to STOP protocol. The difference was significant in TAMM velocity between two groups, with all children being within normal range in group II. Result of this study differs from previous studies, done in western countries probably due to difference in haplotype.

Recommendation to reality: Closing the transcranial Doppler screening gap for children with sickle cell anemia

Although annual transcranial Doppler (TCD) screening is recommended for children with sickle cell anemia (SCA), compliance is low and variable. Our objective was to utilize an electronic health record (EHR)-based registry to improve TCD adherence among children with SCA, 2-16years of age, at our institution. We developed an in-EPIC real time registry for children with sickle cell disease in year 2016. Since end of year 2016, we have been extracting data quarterly to examine TCD rates and share the list of children who have not received a TCD screen in the past 18months with the clinical team. The registry also includes a TCD risk score to enhance point of care. We also added Child Life support to increase TCD compliance among children <7years. Control charts are used to examine TCD rates. At baseline, prior to and start of quarterly data audit and feedback, 63% of children received the recommended annual TCD screen. TCD rates steadily increased to 80% by the third quarter of 2017. We observed a dip in TCD rates, driven by failure of screening young children. Since the initiation of Child Life support for children <7years, we have sustained TCD screen rates >70%. Overall, our data meet criteria for special cause variation, indicating improvement in TCD rates since 2015. Regular tracking and identification of patients overdue for a TCD screen using an EHR-based registry resulted in sustained improvement in TCD screening rates. Involvement of Child Life support further improved TCD rates.