The relationship between cumulative risk and health-related quality of life in youth with sickle cell disease: Moderating effects of secondary control engagement coping.

BACKGROUND: Youth with sickle cell disease (SCD) often experience low health-related quality of life (HRQOL). Engagement in resilience-promoting processes, such as secondary control engagement (SCE) coping, or adapting to stressors, may be linked to contextual risk factors (e.g., poverty status). This study aims to illuminate relationships between a cumulative risk index (CRI), SCE coping, and HRQOL in youth with SCD and test whether SCE coping moderates the relationship between CRI and HRQOL. PROCEDURE: Participants in this cross-sectional study included 63 youth ages 8-18 with SCD. Participants completed measures to assess SCE coping use (Responses to Stress Questionnaire) and HRQOL (PedsQL SCD Module). Six variables from the electronic medical record were compiled in a CRI. Correlational and regression analyses examined relationships between primary variables and moderating effects of SCE coping, respectively. RESULTS: Model results show that SCE coping and CRI explain variation in HRQOL (p = .001), and a significant interaction exists between SCE and CRI (ß = -.29, p = .02), with a stronger inverse relationship between CRI and HRQOL for higher SCE values. This suggests that lower CRI is associated with greater HRQOL for those with higher SCE coping relative to lower SCE coping. CONCLUSIONS: SCE coping may selectively benefit children with SCD experiencing lower cumulative risk, warranting encouragement of this strategy in clinical settings. Findings do not support SCE coping benefits for youth with higher risk, suggesting that the strategy may not be useful when risk-related stressors are especially pervasive; alternative protective factors should be identified for this risk group.

CHOICES for sickle cell reproductive health: A protocol of a randomized preconception intervention model for a single gene disorder.

Our long-term goal is to foster genetically informed reproductive health knowledge and behaviors among young adults with sickle cell disease (SCD) or sickle cell trait (SCT) with a web-based, tailored, multimedia intervention called CHOICES. CHOICES is designed to help young adults with SCD or SCT preconception to gain knowledge of genetic inheritance, specify their reproductive health intentions (their parenting plan), and engage in reproductive health behaviors concordant with their parenting plan. In a previous study, we found high acceptability of both the e-Book (usual care control) and CHOICES interventions. We also found sustained (24 months), significant effects on knowledge but not on behavior, most likely because half of the recruited group was not at risk for their children inheriting SCD. Hence, we propose an adequately powered randomized controlled trial with the CHOICES intervention and an e-Book control to compare their effects on genetic inheritance knowledge and at-risk reproductive health behaviors (immediate posttest and at 6, 12, 18, and 24 months). We will conduct subgroup analyses to provide insight into the baseline knowledge and behavior as well as the intervention effects in different demographic or acceptability groups. Given the scalability and low cost of CHOICES, if proved to be effective, it can reach the affected population at low cost.

The Association Between Caregiver Coping and Youth Clinic Attendance and Health-related Quality of Life in Pediatric Sickle Cell Disease.

Caregivers of youth with sickle cell disease (SCD) influence the youth disease management and psychosocial outcomes. Effective caregiver coping is important for improving disease management and outcomes since caregivers often report high disease-related parenting stress. This study characterizes caregiver coping and examines its relation to youth clinic nonattendance and health-related quality of life (HRQOL). Participants were 63 youth with SCD and their caregivers. Caregivers completed the Responses to Stress Questionnaire-SCD module to assess primary control engagement (PCE; attempts to change stressors or reactions to stress), secondary control engagement (SCE; strategies to adapt to stress), and disengagement (avoidance) coping. Youth with SCD completed the Pediatric Quality of Life Inventory-SCD module. Medical records were reviewed for the hematology appointment nonattendance rates. Coping factors were significantly different ( F [1.837, 113.924]=86.071, P <0.001); caregivers reported more PCE ( M =2.75, SD =0.66) and SCE ( M =2.78, SD =0.66) than disengagement ( M =1.75, SD =0.54) coping. Responses to short-answer questions corroborated this pattern. Greater caregiver PCE coping was associated with lower youth nonattendance (ß=-0.28, P =0.050), and greater caregiver SCE coping was related to higher youth HRQOL (ß=0.28, P =0.045). Caregiver coping is related to improved clinic attendance and HRQOL in pediatric SCD. Providers should assess caregiver coping styles and consider encouraging engagement coping.

The Role of Sleep-Disordered Breathing Symptoms in Neurocognitive Function Among Youth With Sickle Cell Disease.

OBJECTIVE: To examine associations between sleep-disordered breathing (SDB) and executive/attentional function in pediatric sickle cell disease (SCD). METHODS: Sixty youth with SCD ages 8-18 years and caregivers completed the Pediatric Sleep Questionnaire (PSQ), Delis Kaplan Executive Function System Trail Making Test (DKEFS TMT), Psychomotor Vigilance Test (PVT), and the Behavior Rating Inventory Of Executive Function, Second Edition (BRIEF-2) Parent Report. RESULTS: The PSQ significantly predicted the BRIEF-2 Parent Report, F(1, 58) = 44.64, p < .001, R2 = 0.44, f2 = 0.77. CONCLUSIONS: Sleep-disordered breathing symptoms may predict informant-rated executive dysfunction in pediatric SCD, but not performance-based executive function.

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.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Romiplostim as a Therapeutic Intervention for Tacrolimus-induced Immune Thrombocytopenia in a Pediatric Cardiac Transplant Patient.

Tacrolimus-induced immune thrombocytopenia (ITP) is a rare entity that can occur years after initiation of tacrolimus therapy following solid organ transplantation, and platelet recovery can be substantially delayed following discontinuation of tacrolimus. Romiplostim, a thrombopoietin receptor agonist approved by the FDA in 2018 for the treatment of chronic ITP in children, may be a useful therapy to hasten platelet recovery in the acute ITP setting in place of immunomodulating agents. We present a case of tacrolimus-induced ITP successfully treated with romiplostim in a child following cardiac transplantation.

Spirometry use in Patients with Sickle Cell Disease with and without asthma and acute chest syndrome: A Multicenter Study.

A de-identified data repository of electronic medical record (EMR) data, i2b2 (Informatics for Integrating Biology and the Bedside), including 4 geographically diverse academic medical centers, was queried to determine the use of diagnostic spirometry testing in African American children and young adults 5-34 years old with sickle cell disease (SCD) with or without a documented history of asthma and/or acute chest syndrome (ACS). A total of 2,749 patients were identified with SCD, of these 577 had asthma and 409 had ACS. Cross-referencing the CPT code for diagnostic spirometry showed that for patients identified as having SCD, a history or ACS, and a diagnosis of asthma, only 31% across all 4 centers had spirometry. Having an asthma diagnosis was associated with ACS. Among SCD patients with asthma, the proportion with ACS for the four centers was 47%, 75%, 38%, and 36% respectively. The bivariate association between asthma and ACS for each Center was significant for each (p<.001). To summarize, only one third of patients with co-morbid SCD, ACS, and asthma received the spirometry procedure as recommended in evidence-based guidelines, suggesting limited testing for changes in pulmonary function. Future studies to determine barriers and facilitators to implementation of pulmonary testing in SCD are warranted.

Feasibility and preliminary outcomes of an integrated pediatric sickle cell disease and pulmonary care clinic for children with sickle cell disease.

BACKGROUND: In children with sickle cell disease (SCD), comorbid asthma is associated with increased disease severity and morbidity, but it remains underdiagnosed and optimal management paradigms are not well defined. The purpose of this study was to determine the feasibility and preliminary outcomes of an integrated pediatric SCD and pulmonary care clinic in children with SCD. METHODS: We implemented a pre-post quality improvement (QI) project in our pediatric hematology clinic between 2017 and 2019. Guided by the chronic care model, patients who were ages 2-18 years, diagnosed with SCD and suspected pulmonary comorbidities, received care in an interdisciplinary clinic. We examined feasibility and compared clinical outcomes to 24 months prior (2015-2017) to the implementation of the integrated care model. RESULTS: Twenty-four patients were included in the QI project: 88% (n = 21) received pulmonary function testing, 92% (n = 22) were diagnosed with asthma, and 33% (n = 8) with obstructive sleep apnea. Adherence to pulmonary appointments was increased by 81% (mean difference [MD] = 1.3, 95% confidence interval [CI] = 0.71-1.92; P < .001). Unplanned acute health care utilization was reduced by 59% (MD = 2.9, 95% CI = 1.14-4.69; P < .01) and packed red blood cell transfusion was reduced by 81% (MD = 1.38, 95% CI = 0.71-2.04; P < .001). CONCLUSION: Asthma is prevalent in children with SCD, and interdisciplinary clinics can improve access to subspecialty pulmonary care and reduce unplanned acute care. Additional patients and a longer follow-up period are required to determine the true treatment effect.

Life-Threatening Infectious Complications in Sickle Cell Disease: A Concise Narrative Review.

Sickle cell disease (SCD) results in chronic hemolytic anemia, recurrent vascular occlusion, insidious vital organ deterioration, early mortality, and diminished quality of life. Life-threatening acute physiologic crises may occur on a background of progressive diminishing vital organ function. Sickle hemoglobin polymerizes in the deoxygenated state, resulting in erythrocyte membrane deformation, vascular occlusion, and hemolysis. Vascular occlusion and increased blood viscosity results in functional asplenia and immune deficiency in early childhood, resulting in life-long increased susceptibility to serious bacterial infections. Infection remains a main cause of overall mortality in patients with SCD in low- and middle-income countries due to increased exposure to pathogens, increased co-morbidities such as malnutrition, lower vaccination rates, and diminished access to definitive care, including antibiotics and blood. Thus, the greatest gains in preventing infection-associated mortality can be achieved by addressing these factors for SCD patients in austere environments. In contrast, in high-income countries, perinatal diagnosis of SCD, antimicrobial prophylaxis, vaccination, aggressive use of antibiotics for febrile episodes, and the availability of contemporary critical care resources have resulted in a significant reduction in deaths from infection; however, chronic organ injury is problematic. All clinicians, regardless of their discipline, who assume the care of SCD patients must understand the importance of infectious disease as a contributor to death and disability. In this concise narrative review, we summarize the data that describes the importance of infectious diseases as a contributor to death and disability in SCD and discuss pathophysiology, prevalent organisms, prevention, management of acute episodes of critical illness, and ongoing care.

Splenectomy to Optimize Hemoglobin S Control in Children With Sickle Cell Anemia on Chronic Transfusion Therapy for Stroke Prevention.

Chronic transfusion therapy with the goal of maintaining a hemoglobin (Hb) S <30% is the primary recommended treatment for children with sickle cell anemia and a history of overt stroke or abnormal transcranial Doppler examination. We report chronic hypersplenism as a cause of poor HbS% control in 3 children on chronic transfusion therapy for stroke prevention. Splenectomy resulted in a 39.77% (95% confidence interval, 34.3-45.3, P<0.0001) mean reduction in HbS% with no perioperative or infectious complications suggesting the need for additional research into splenectomy as a therapeutic option for select high-risk children to optimize transfusion therapy for stroke prevention.

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial).

Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated the effect of 3 different doses of SC411 on clinical and biochemical endpoints in 67 children with SCD (5-17 years old). Seventy-six percent of subjects were also receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg DHA/kg per day or placebo a statistically significant (P < .001) mean percentage increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs baseline: 109.0% (confidence interval [CI], 46.7-171.3), 163.8% (CI, 108.3-219.2), 170.8% (CI, 90.2-251.4), and 28.6% (CI, 250.1 to 107.3), respectively. After 8 weeks of treatment, statistically significant changes vs placebo were also observed in D-dimer (P = .025) and soluble E-selectin (P = .0219) in subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411 significantly reduced electronic diary recorded SCC, analgesic use at home, and days absent from school because of sickle cell pain. The lower rate of clinical SCC observed in the pooled active groups vs placebo did not reach statistical significance (rate ratio, 0.47; 95% CI, 0.20-1.11; P = .07). All tested doses were safe and well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02973360.

Effects of oxytocin and prolactin on stress-induced bladder hypersensitivity in female rats.

UNLABELLED: Anecdotal evidence suggests that chronic bladder pain improves while breastfeeding. The present study sought to identify potential mechanisms for such a phenomenon by investigating the effects of the lactogenic hormones prolactin (PL) and oxytocin (OXY) in a rat model of bladder nociception. Lactating rats were less sensitive to urinary bladder distension (UBD) than controls. In investigating potential antinociceptive and anxiolytic roles for these hormones, we found exposure to a footshock paradigm (STRESS groups) produced bladder hypersensitivity in saline-treated rats, manifested as significantly higher electromyographical (EMG) responses to UBD, compared to rats exposed to a nonfootshock paradigm (SHAM groups). This hypersensitivity was attenuated by the intraperitoneal administration of OXY prior to footshock in the STRESS-OXY group. The administration of PL augmented EMG responses in the SHAM-PL group but had no effect on the responses of the STRESS-PL group. In the absence of behavioral pretreatment, OXY attenuated UBD-evoked responses while PL had no effect. Moreover, OXY-treated rats spent more time in the open arm of an elevated plus maze compared to saline-treated rats suggesting anxiolysis. These studies suggest the potential for systemic OXY, but not PL, as an analgesic and anxiolytic treatment for painful bladder disorders such as interstitial cystitis. PERSPECTIVE: This study presents evidence that systemic oxytocin has both analgesic and anxiolytic properties which may make it a potentially useful agent for patients with stress-exacerbated chronic-pain syndromes such as interstitial cystitis. These studies do not suggest a similar role for prolactin.

Disorders of the fetomaternal unit: hematologic manifestations in the fetus and neonate.

Histoarchitectural characteristics of the human placenta place the fetus at a high risk of growth restriction, abnormal fetomaternal cell traffic, and vertical transmission of pathogens. These abnormalities of the fetomaternal unit are frequently associated with hematological abnormalities in the fetus/neonate and may be the first, most common, or the only clinical manifestations of these conditions. This article reviews the pathophysiology and characteristic hematological manifestations of these conditions in the fetus and the neonate.

Shwachman-Diamond syndrome presenting in a premature infant as pancytopenia.

Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized by bone marrow dysfunction, exocrine pancreatic insufficiency, failure to thrive, and skeletal abnormalities. It is most commonly diagnosed in early childhood after the development of hematologic abnormalities. We report a premature infant born at 33 weeks gestation who was small for gestational age and displayed persistent cytopenias requiring transfusion. Genetic testing confirmed a diagnosis of Shwachman-Diamond syndrome (SDS).