An investigation of vascular anomalies centers' transition of care practices.

This study aims to examine transition of care (TOC) practices of multidisciplinary vascular anomalies centers (VACs). Thirty-seven of 71 VAC leaders to whom the survey was sent completed the questionnaire. TOC and transfer practices varied with only 16% of VACs having TOC programs. The most frequently cited barriers to developing a TOC program were lack of resources and difficulty finding expert adult providers.

Acute chest syndrome, airway inflammation and lung function in sickle cell disease.

BACKGROUND: Acute chest syndrome (ACS) is an acute complication in SCD but its effects on lung function are not well understood. Inflammation is a key component of SCD pathophysiology but with an unclear association with lung function. We hypothesized that children with ACS had worse lung function than children without ACS and aimed to investigate the association of lung function deficits with inflammatory cytokines. METHODS: Patients enrolled in a previous 2-year randomized clinical trial who had consented to future data use, were enrolled for the present exploratory study. Patients were categorized into ACS and non-ACS groups. Demographic and clinical information were collected. Serum samples were used for quantification of serum cytokines and leukotriene B4 levels and pulmonary function tests (PFTs) were assessed. RESULTS: Children with ACS had lower total lung capacity (TLC) at baseline and at 2 years, with a significant decline in forced expiratory volume in 1 sec (FEV1) and mid-maximal expiratory flow rate (FEF25-75%) in the 2 year period (p = 0.015 and p = 0.039 respectively). For children with ACS, serum cytokines IL-5, and IL-13 were higher at baseline and at 2 years compared to children with no ACS. IP-10 and IL-6 were negatively correlated with PFT markers. In multivariable regression using generalized estimating equation approach for factors predicting lung function, age was significantly associated FEV1 (p = 0.047) and ratio of FEV1 and forced vital capacity (FVC)- FEV1/FVC ratio (p = 0.006); males had lower FEV1/FVC (p = 0.035) and higher TLC (p = 0.031). Asthma status was associated with FEV1 (p = 0.017) and FVC (p = 0.022); history of ACS was significantly associated with TLC (p = 0.027). CONCLUSION: Pulmonary function abnormalities were more common and inflammatory markers were elevated in patients with ACS, compared with those without ACS. These findings suggest airway inflammation is present in children with SCD and ACS, which could be contributing to impaired pulmonary function.

Sickle cell disease in the new era: advances in drug treatment.

Sickle cell disease is an inherited blood disorder afflicting an estimated 100,000 individuals in the United States and over 20 million people worldwide. The disease is heralded as the first molecular disease. However, despite its genetic simplicity, the pathophysiologic processes leading to its clinical sequelae are complex, heterogeneous and interrelated, making drug development to treat the disease challenging. For over two decades only one drug, hydroxyurea, had been used as disease-modifying therapy. New pharmacologic agents are rapidly evolving with three new drugs, with different mechanisms of action, approved by the United States Food and Drug Administration in recent years (L-glutamine, crizanlizumab and voxelotor). Several therapeutic approaches targeting different pathways in the disease pathophysiology are being investigated. These include inhibition of hemoglobin S polymerization such as by fetal hemoglobin induction or by increasing hemoglobin oxygen affinity, as well as intervention of downstream pathways including inhibiting cellular adhesion, reducing inflammation and oxidant stress, modulating platelet activation and coagulation abnormalities, and targeting nitric oxide signaling. This review will provide an overview of these therapeutic strategies, discuss the four currently approved drugs in detail, and summarize ongoing clinical trials of new drugs or drug indications for the treatment of sickle cell disease in different phases of development excluding those related to cellular therapies.

Food insecurity, housing instability, and dietary quality among children with sickle cell disease: Assessment from a single urban center.

BACKGROUND: Food insecurity and housing instability, both social determinants of health (SDoH), disproportionately affect economically unstable, under-resourced US communities in which children with sickle cell disease (SCD) live. Association between these SDoH markers and dietary quality among children with SCD is unknown. PROCEDURES: We assessed a cross-sectional sample of dyadic parent-child patients and young adult patients up to age 21 from one pediatric SCD center. Food insecurity, housing instability, and dietary quality were measured using validated US instruments and a food frequency questionnaire. Better dietary quality was defined using US dietary guidelines. Multivariate regression assessed for associations among dietary quality and food insecurity with or without (±) housing instability and housing instability alone. RESULTS: Of 100 enrolled participants, 53% were Black and 43% Hispanic; mean age 10.6 ± 5.6 years. Overall, 70% reported less than or equal to one economic instability: 40% housing instability alone and 30% both food insecurity and housing instability. Eighty percent received more than or equal to one federal food assistance benefit. Compared to no economic instability, food insecurity ± housing instability was significantly associated with higher intake of higher dairy and pizza, while housing instability alone was significantly associated with higher dairy intake. Food insecurity ± housing instability was significantly associated with lower intake of whole grains compared to housing instability alone. CONCLUSIONS: Our sample reported high frequencies of both food insecurity and housing instability; having more than or equal to one SDoH was associated with elements of poorer diet quality. Screening families of children with SCD for food insecurity and housing instability may identify those with potential nutrition-related social needs.

Validation of a Questionnaire to Identify Respiratory Tract Infections in Children With Sickle Cell Disease.

BACKGROUND: No validated questionnaires have been published that are specific for identifying respiratory infections in children with sickle cell disease (SCD). METHODS: A questionnaire was developed that included 6 respiratory symptoms (difficulty breathing, wheezing, fever, cough, runny or stuffy nose, and sore throat) to identify respiratory events for a clinical trial. The questionnaire results were compared with identification of viral respiratory pathogens from nasal samples by reverse transcriptase polymerase chain reaction. RESULTS: Eighty questionnaire responses (40 with symptom/s and 40 without) paired with isolation of viral respiratory pathogen from nasal samples were obtained from 53 children with SCD, ages 4 to 18 years over 2 separate periods in different seasons. The questionnaire yielded a sensitivity of 82%, specificity of 72% with an overall accuracy of 76%. The kappa value was 0.53, indicating moderate agreement, and the Fleiss' kappa test statistic was 4.77 with P<0.001, indicating that agreement between the 2 methods was not by chance. CONCLUSION: These results provide evidence for validity of this 6-symptom respiratory questionnaire in identification of respiratory viral infections for use in SCD-related research.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.

Impact of recovery support navigators on continuity of care after detoxification.

Although evidence points to the benefits of continuity of care after detoxification (detox), especially when continuity of care occurs within a short time after discharge from a detox episode, the rate at which clients engage in continued treatment after detox remains low. The goal of the study was to develop and deploy a specially trained workforce, called recovery support navigators (RSNs), to increase the likelihood of clients continuing onto treatment after detox. Continuity of care is defined as receiving any substance use disorder (SUD) treatment service within 14 days of discharge from the index detox. We examined whether clients in the RSN Intervention group were more likely to meet the continuity of care after detox criteria than clients in the treatment-as-usual (TAU) group. A quasi-experimental intervention versus comparison group study was conducted. Data were from the Massachusetts Behavioral Health Partnership (MBHP), a Beacon Health Options company that manages behavioral health benefits for a subset of Medicaid beneficiaries in the state. Inclusion in the analytic sample (N = 4,236) required that the client's index admission to detox was between 3/29/13 and 3/31/15. RSN Intervention versus TAU status was assigned based on provider organization where the index detox occurred. Analyses were conducted on an intent-to-treat basis. Overall, the continuity of care rate across all study groups was 42%. The rate by study group was 38% for the TAU and 45% for the RSN group. Clients who were in the RSN group were significantly more likely to have continuity of care after discharge from detox than those in the TAU (OR = 1.233, p < .05, 95% CI = 1.044, 1.455). Clients who entered detox at a site that provided specialized training to RSN, which included motivational interviewing and educational sessions related to treatment issues, and allowing them to bill with a flexible daily case rate instead of the usual fee-for-service billing, were more likely to have continuity of care after discharge from detox compared to clients in the TAU group.

Acupuncture for pediatric sickle cell pain management: A promising non-opioid therapy.

OBJECTIVE: To describe the use of acupuncture for pain management in children with sickle cell disease. DESIGN: A retrospective chart review of a single-institution experience on the use of acupuncture in pediatric patients with sickle cell disease was evaluated between 2012-2019. Demographic characteristics, presenting pain location, pain scores pre- and post-acupuncture, and adverse events were collected. SETTING: Columbia University Medical Center, NewYork-Presbyterian Morgan Stanley Children's Hospital Pediatric Hematology outpatient and inpatient units. INTERVENTIONS: Acupuncture was performed by six licensed acupuncturists. Point prescriptions were based on pain location, philosophies of Traditional Chinese Medicine and Japanese Style of Kiiko Matsumoto acupuncture. MAIN OUTCOME MEASURES: Pain reduction as measured by two Verbal Pain Scales. RESULTS: Ninety acupuncture treatments were administered to twenty-four patients with sickle cell disease: median age 17.5 years, 62 % female, 37.5 % African American, 50 % Hispanic. The mean treatment duration was 18.5 ±â€¯4.8 min. Fifty-five treatments had documented pre/post-acupuncture pain scores. Pain reduction was achieved in 65.5 % of these treatments. A 0-10 pain scale used in 13 treatments reported a mean pre-acupuncture score of 7.31 ±â€¯1.75, post-acupuncture score of 6.08 ±â€¯1.85, and a mean pain score change of 1.23 ±â€¯1.09 (p = 0.11); A 0-4 pain scale used in 42 treatments reported a mean pre-acupuncture pain score of 3.31 ±â€¯0.72, post-acupuncture score of 2.33 ±â€¯0.98, and a mean pain score change of 0.98 ±â€¯0.99 (p < 0.0001). No adverse events were noted. CONCLUSION: Acupuncture therapy decreased pain for our patients with sickle cell disease, providing a safe non-opioid therapeutic option.

Rural Clients' Continuity Into Follow-Up Substance Use Disorder Treatment: Impacts of Travel Time, Incentives, and Alerts.

PURPOSE: Treatment after discharge from detoxification or residential treatment is associated with improved outcomes. We examined the influence of travel time on continuity into follow-up treatment and whether financial incentives and weekly alerts have a modifying effect. METHODS: For a research intervention during October 2013 to December 2015, detoxification and residential substance use disorder treatment programs in Washington State were randomized into 4 groups: potential financial incentives for meeting performance goals, weekly alerts to providers, both interventions, and control. Travel time was used as both a main effect and interacted with other variables to explore its modifying impact on continuity of care in conjunction with incentives or alerts. Continuity was defined as follow-up care occurring within 14 days of discharge from detoxification or residential treatment programs. Travel time was estimated as driving time from clients' home ZIP Code to treatment agency ZIP Code. FINDINGS: Travel times to the original treatment agency were in some cases significant with longer travel times predicting lower likelihood of continuity. For detoxification clients, those with longer travel times (over 91 minutes from their residence) are more likely to have timely continuity. Conversely, residential clients with travel times of more than 1 hour are less likely to have timely continuity. Interventions such as alerts or incentives for performance had some mitigating effects on these results. Travel times to the closest agency for potential further treatment were not significant. CONCLUSIONS: Among rural clients discharged from detoxification and residential treatment, travel time can be an important factor in predicting timely continuity.

Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease.

In sickle cell disease, respiratory infection and asthma may lead to respiratory complications that are a leading cause of morbidity and mortality. Vitamin D has anti-infective and immunomodulatory effects that may decrease the risk for respiratory infections, asthma, and acute chest syndrome. We conducted a randomized double-blind active-controlled clinical trial to determine whether monthly oral vitamin D3 can reduce the rate of respiratory events in children with sickle cell disease. Seventy sickle cell subjects, ages 3-20 years, with baseline records of respiratory events over 1 year before randomization, underwent screening. Sixty-two subjects with 25-hydroxyvitamin D levels of 5-60 ng/mL were randomly assigned to oral vitamin D3 (100 000 IU or 12 000 IU, n = 31 each) under observed administration once monthly for 2 years. The primary outcome was the annual rate of respiratory events (respiratory infection, asthma exacerbation, or acute chest syndrome) ascertained by the use of a validated questionnaire administered biweekly. Analysis included 62 children (mean age of 9.9 years, 52% female, and predominantly with homozygous HbS disease [87%]) with mean baseline 25-hydroxyvitamin D of 14.3 ng/mL. The annual rates of respiratory events at baseline and intervention years 1 and 2 were 4.34 ± 0.35, 4.28 ± 0.36, and 1.49 ± 0.37 (high dose) and 3.91 ± 0.35, 3.34 ± 0.37, and 1.54 ± 0.37 (standard dose), respectively. In pediatric patients with sickle cell disease, 2-year monthly oral vitamin D3 was associated with a >50% reduction in the rate of respiratory illness during the second year (P = .0005), with similar decreases associated with high- and standard-dose treatment. This trial was registered at www.clinicaltrials.gov as #NCT01443728.

Impact of Agency Receipt of Incentives and Reminders on Engagement and Continuity of Care for Clients With Co-Occurring Disorders.

OBJECTIVE: This study examined whether having co-occurring substance use and mental disorders influenced treatment engagement or continuity of care and whether offering financial incentives, client-specific electronic reminders, or a combination to treatment agencies improved treatment engagement and continuity of care among clients with co-occurring disorders. METHODS: The study used a randomized cluster design to assign agencies (N=196) providing publicly funded substance use disorder treatment in Washington State to a research arm: incentives only, reminders only, incentives and reminders, and a control condition. Data were analyzed for 76,044 outpatient, 32,797 residential, and 39,006 detoxification admissions from Washington's treatment data system. Multilevel logistic regressions were conducted, with clients nested within agencies, to examine the effect of the interventions on treatment engagement and continuity of care. RESULTS: Compared with clients with a substance use disorder only, clients with co-occurring disorders were less likely to engage in outpatient treatment or have continuity of care after discharge from residential treatment, but they were more likely to have continuity of care after discharge from detoxification. The interventions did not influence treatment engagement or continuity of care, except the reminders had a positive impact on continuity of care after residential treatment among clients with co-occurring disorders. CONCLUSIONS: In general, the interventions did not result in improved treatment engagement or continuity of care. The limited number of significant results supporting the influence of incentives and alerts on treatment engagement and continuity of care add to the mixed findings reported by previous research. Multiple interventions may be needed for performance improvement.

Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease.

Patients with sickle cell disease (SCD) are at risk for bone fragility from multiple factors including vitamin D deficiency. To date, no studies have evaluated the efficacy and safety of long-term vitamin D therapy for bone disease in children with SCD. We report a cohort of 4 children with SCD found to have severe vitamin D deficiency, secondary hyperparathyroidism, and abnormal bone mineral density treated with monthly high-dose oral cholecalciferol over 2 years. All patients exhibited a positive response to therapy without hypervitaminosis D or hypercalcemia. Further studies are needed to standardize guidelines for optimal vitamin D dosing and prevention of toxicity.

Agency-level financial incentives and electronic reminders to improve continuity of care after discharge from residential treatment and detoxification.

BACKGROUND: Despite the importance of continuity of care after detoxification and residential treatment, many clients do not receive further treatment services after discharged. This study examined whether offering financial incentives and providing client-specific electronic reminders to treatment agencies lead to improved continuity of care after detoxification or residential treatment. METHODS: Residential (N = 33) and detoxification agencies (N = 12) receiving public funding in Washington State were randomized into receiving one, both, or none (control group) of the interventions. Agencies assigned to incentives arms could earn financial rewards based on their continuity of care rates relative to a benchmark or based on improvement. Agencies assigned to electronic reminders arms received weekly information on recently discharged clients who had not yet received follow-up treatment. Difference-in-difference regressions controlling for client and agency characteristics tested the effectiveness of these interventions on continuity of care. RESULTS: During the intervention period, 24,347 clients received detoxification services and 20,685 received residential treatment. Overall, neither financial incentives nor electronic reminders had an effect on the likelihood of continuity of care. The interventions did have an effect among residential treatment agencies which had higher continuity of care rates at baseline. CONCLUSIONS: Implementation of agency-level financial incentives and electronic reminders did not result in improvements in continuity of care, except among higher performing agencies. Alternative strategies at the facility and systems levels should be explored to identify ways to increase continuity of care rates in specialty settings, especially for low performing agencies.

Influencing quality of outpatient SUD care: Implementation of alerts and incentives in Washington State.

Financial incentives for quality improvement and feedback on specific clients are two approaches to improving the quality of treatment for individuals with substance use disorders. We examined the impacts of these interventions in Washington State by randomizing outpatient substance use treatment agencies into intervention and control groups. From October 2013 through December 2015, agencies could earn financial incentives for meeting performance goals incorporating both achievement relative to a benchmark and improvement from agencies' own baselines. Weekly feedback was e-mailed to agencies in the alert or alert plus incentives arms. Difference-in difference regressions controlling for client and agency characteristics showed that none of the interventions significantly affected client engagement after outpatient admissions, overall or for sub-groups based on race/ethnicity, age, rural residence, or agency baseline performance. Treatment agencies offered insights related to several themes: delivery system context (e.g., agency time and resources needed during transition to a managed behavioral healthcare system), implementation (e.g., data lag), agency issues (e.g., staff turnover), and client factors (e.g., motivation). Interventions took place during a time of Medicaid expansion and planning for statewide integration of mental health and substance use disorder treatment into a managed care model, which may have resulted in agencies not responding to the interventions. Moreover, incentives and alerts at the agency-level may not be effective when factors are at play beyond the agency's control.

Longitudinal Analysis of Echocardiographic Abnormalities in Children With Sickle Cell Disease.

BACKGROUND: Cardiac abnormalities have been described in echocardiograms of children with sickle cell disease (SCD). However, longitudinal studies investigating progression of echocardiographic abnormalities across the pediatric age spectrum in SCD are lacking. METHODS: A retrospective longitudinal analysis of 829 echocardiograms from pediatric patients with SCD at steady-state was performed. Left heart parameters included left ventricular end-systolic, end-diastolic diameters, fractional shortening, and mass. Right ventricular pressure was estimated by tricuspid regurgitation gradient. Tricuspid regurgitation gradient ≥25 mm Hg, a z-score ≥2 for LV parameters and ≤-2 for left ventricular fractional shortening were considered abnormal. RESULTS: Kaplan-Meier analysis revealed that echocardiographic abnormalities were detected by 5 years of age, and the cumulative incidence progressively increased throughout childhood. Age, male gender, HbSS and Sß thalassemia genotype, white blood cell count, platelet count, total bilirubin, admissions for pain crises and acute chest syndrome were positively, whereas hemoglobin was negatively associated with cardiac abnormalities. CONCLUSION: Cardiac abnormalities began early in childhood and progressively increased with age. Our study highlights the high cumulative incidence of cardiac abnormalities in children with SCD, which could represent a marker of disease severity.

Optical Coherence Tomography Angiography and Ultra-widefield Fluorescein Angiography for Early Detection of Adolescent Sickle Retinopathy.

PURPOSE: Based on standard screening techniques, sickle retinopathy reportedly occurs in 10% of adolescents with sickle cell disease (SCD). We performed a prospective, observational clinical study to determine if ultra-widefield fluorescein angiography (UWFA), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCT-A) detect more-frequent retinopathy in adolescents with SCD. DESIGN: Cross-sectional study. METHODS: Setting: Institutional. SUBJECTS: Sixteen adolescents with SCD, aged 10-19 years (mean age 14.9 years), and 5 age-equivalent controls (mean age 17.4 years). OBSERVATION PROCEDURES: Examinations including acuity, standard slit-lamp biomicroscopy, UWFA, SD-OCT, and OCT-A were performed. MAIN OUTCOME MEASURES: Sickle retinopathy defined by biomicroscopic changes, Goldberg stages I-V, Penman scale, flow void on OCT-A, or macular thinning on SD-OCT. RESULTS: While 22 of 32 SCD eyes (68.8%) had retinopathy on biomicroscopy, by UWFA 4 of 24 (16.7%) SCD eyes had peripheral arterial occlusion (Goldberg I), and 20 of 24 eyes (83.3%) had peripheral arteriovenous anastomoses (Goldberg II) in addition. No patients had Goldberg stages III-V. By SD-OCT and OCT-A, thinning of the macula and flow voids in both the superficial and deep retinal capillary plexus were found in 6 of 30 (20%) eyes. CONCLUSIONS: All 24 eyes with adequate UWFA studies demonstrated sickle retinopathy. SD-OCT and OCT-A, which have not been previously reported in the adolescent population, detected abnormal macular thinning and flow abnormalities undetected by biomicroscopy. These findings suggest that pediatric sickle retinopathy may be more prevalent than previously suspected. If these findings are confirmed with larger cross-sectional and prospective analyses, these approaches may enhance early screening for sickle retinopathy.

Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.

Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.