Investigating home-based opioid use among youth with sickle cell disease using ecological momentary assessment.

Background: Opioids are a common and essential treatment for acute sickle cell disease (SCD) pain. However, opioids carry well-known adverse side effects, including potential development of hyperalgesia and nociplastic pain. We characterized opioid use in youth with SCD using ecological momentary assessment (EMA) data, and investigated the relationships between home-based opioid use, pain, and a range of biopsychosocial factors.

Psychosis secondary to COVID-19 in pediatric sickle cell disease.

Key Clinical Message: COVID-19 psychosis is a potential long-term sequela of COVID-19. Vulnerable populations, such as individuals with sickle cell disease, are at high risk for psychosis. Given the limited number of cases, more investigations in the etiopathology and management of this new disease is needed.

Efficacy and safety in patients with haemophilia A switching to octocog alfa (BAY 81-8973): Final results of the global real-world study, TAURUS.

Objectives: To report the final results of the 2-year TAURUS study, assessing weekly prophylaxis dosing regimens of octocog alfa (Kovaltry®/BAY 81-8973) used in standard clinical practice in patients with moderate-to-severe haemophilia A.

Methods: TAURUS (NCT02830477) is a phase 4, multinational, prospective, non-interventional, single-arm study in patients of any age with moderate or severe haemophilia A (≤5% factor [F]VIII activity). TAURUS was designed to primarily investigate weekly prophylaxis dosing regimens used in standard clinical practice.

A randomized, placebo-controlled, double-blind trial of canakinumab in children and young adults with sickle cell anemia.

Excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) in patients with sickle cell anemia (SCA) can activate the inflammasome, a multiprotein oligomer promoting maturation and secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). We hypothesized that IL-1β blockade by canakinumab in patients with SCA would reduce markers of inflammation and clinical disease activity. In this randomized, double-blind, multicenter phase 2a study, patients aged 8 to 20 years with SCA (HbSS or HbSβ0-thalassemia), history of acute pain episodes, and elevated high-sensitivity C-reactive protein >1.

Pediatric sickle cell pain-sleep relationships: The roles of positive and negative affect.

Objective: The current study investigated the role of affect in the daily sleep quality-pain severity relationship in youth with sickle cell disease (SCD). Previous investigations have not allowed researchers to examine whether positive and negative affect work differentially in their relations with pediatric SCD pain, sleep, and the sleep-pain relationship. The current study focused on examining the possible mediating and moderating roles positive and negative affect have in the sleep-pain relationship for youth with SCD.

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.

Depression and Anxiety as Moderators of the Pain-Social Functioning Relationship in Youth with Sickle Cell Disease.

Purpose: Youth with sickle cell disease (SCD), a genetic disorder of red blood cells, may experience acute pain episodes lasting 2 to 3 days on average. While existing research has demonstrated associations between SCD pain and poor social functioning in youth with SCD, there are no data on whether symptoms of depression and anxiety modify the relationship between pain and functional outcomes in pediatric pain populations. It was hypothesized that more symptoms of depression and anxiety would exacerbate the relationship between high pain and poor social functioning in youth with SCD.

BAY 81-8973 prophylaxis and pharmacokinetics in haemophilia A: Interim results from the TAURUS study.

Objectives: To report interim data from TAURUS, a study assessing real-world prophylactic treatment with unmodified, full-length recombinant FVIII BAY 81-8973 (Kovaltry ; Bayer) indicated for haemophilia A.

Methods: TAURUS (NCT02830477) is an international, open-label, prospective, non-interventional, single-arm study with a one-year observation period (target N = 350). Patients have moderate or severe haemophilia A (FVIII ≤5% or ≤1%) and ≥50 exposure days to any FVIII product.

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.

Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes.

In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first.

Sleep Problem Risk for Adolescents With Sickle Cell Disease: Sociodemographic, Physical, and Disease-related Correlates.

The aims of the current study were to investigate whether SCD incurs an additional risk for poor sleep over and above the influence of sociodemographic factors (ie, race and sex) during adolescence, and to explore the relationships between sociodemographic, physical (ie, age and pubertal status), and disease-related factors (ie, SCD genotype and hydroxyurea use) on sleep problem risk during adolescence. Black adolescents (age, 12 to 17 y) with SCD (n=53) were recruited from regional pediatric SCD clinics in the southeast and a sample of healthy black adolescents (n=160) were recruited from middle and high schools. Regression analyses indicated that SCD was uniquely related to sleeping more, and worse sleep quality over and above the influence of sociodemographic factors.

Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.

Background: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

Methods: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada.

Organ iron accumulation in chronically transfused children with sickle cell anaemia: baseline results from the TWiTCH trial.

Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants.

Experiences of Pediatric Patients With Sickle Cell Disease in Rural Emergency Departments.

Background: The aims of this study were to describe guardian perceptions of the experiences of a sample of youth with sickle cell disease (SCD) in rural emergency departments (EDs) with a focus on overall patient satisfaction and characteristics of care.

Procedure: Guardians of 139 children with SCD (0 to 17 y) seen at a rural pediatric SCD clinic completed a survey concerning their children's ED experiences in the past 6 months, including information about ED wait times, quality of communications and interactions with the ED health care providers, pain management, perceptions of speed of care, and overall satisfaction.

Results: About 41% of guardians reported that their child visited the ED in the past 6 months.

Health-related quality of life in children with sickle cell anemia: impact of blood transfusion therapy.

The completion of the Multicenter Silent Infarct Transfusion Trial demonstrated that children with pre-existing silent cerebral infarct and sickle cell anemia (SCA) who received regular blood transfusion therapy had a 58% relative risk reduction of infarct recurrence when compared to observation. However, the total benefit of blood transfusion therapy, as assessed by the parents, was not measured against the burden of monthly blood transfusion therapy. In this planned ancillary study, we tested the hypothesis that a patient centered outcome, health-related quality of life (HRQL), would be greater in participants randomly assigned to the blood transfusion therapy group than the observation group.

Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia.

Background: Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.

Methods: In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group).

Malignant transformation of infantile hemangioma to angiosarcoma: response to chemotherapy with bevacizumab.

We describe a child initially diagnosed with multi-focal infantile hemangioma (cutaneous, hepatic, pulmonary), a benign vascular lesion, which underwent malignant transformation to angiosarcoma. The use of anti-angiogenic agents, such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has been reported in adults with angiosarcoma. Treatment with chemotherapy (gemcitabine and docetaxel) and bevacizumab resulted in disease response with progression free survival of 12 months.

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure.

The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures.

Bilateral internal carotid artery occlusions in a pediatric patient with refractory acute myeloid leukemia.

Thromboembolism is a well-known complication of cancer including acute myeloid leukemia (AML) especially in patients with high myeloblast counts. However, spontaneous vaso-occlusion in the main arteries is very rare especially in patients with low blast counts and no pre existing vasculopathy. We report the case of a 3-year-old male with refractory AML who developed spontaneous bilateral internal carotid artery occlusion with diffuse cerebral infarcts.

Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells.

The Signal Transducer and Activator of Transcription (STAT) proteins comprise a family of latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth and survival, and its persistent activation has been detected with high frequency in many human cancers. As constitutive activation of STAT3 appears to be vital for the continued survival of these cancerous cells, it has emerged as an attractive target for chemotherapeutics.