Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial.

Background: Sickle cell disease, a debilitating, inherited haemolytic anaemia with premature morbidity and mortality, affects millions globally. Mitapivat, a first-in-class, oral, allosteric activator of pyruvate kinase, improves red blood cell survival by increasing ATP and diminishes sickling by decreasing 2,3-diphosphoglycerate. We aimed to evaluate the efficacy and safety of mitapivat in patients with sickle cell disease.

Statistical significance, clinical importance and effect sizes: Enhancing understanding of a study's results.

Background: The proper interpretation of a study's results requires both excellent understanding of good methodological practices and deep knowledge of prior results, aided by the availability of effect sizes.

Methods: This review takes the form of an expository essay exploring the complex and nuanced relationships among statistical significance, clinical importance, and effect sizes.

Results: Careful attention to study design and methodology will increase the likelihood of obtaining statistical significance and may enhance the ability of investigators/readers to accurately interpret results.

Targeting TRPV1 activity via high-dose capsaicin in patients with sickle cell disease.

Evidence suggests neuropathic pain (NP) develops over time in sickle cell disease (SCD), contributing to a complex, difficult-to-treat phenotype, with management based on scant evidence. One characteristic of NP found is hyperalgesia caused by nervous system sensitization, but risk factors for this have not been identified within the SCD population, as exact mechanisms leading to its development are not well defined. The SPICE (Sickle cell Pain: Intervention with Capsaicin Exposure) trial was a pilot safety and feasibility trial of high-dose (8%) topical capsaicin for patients with SCD and recurrent/chronic pain with neuropathic features, aimed at exploring capsaicin's utility as a mechanistic probe and adjunctive pain treatment for this population.

Prophylactic Hydroxyurea Treatment Is Associated with Improved Cerebral Hemodynamics as a Surrogate Marker of Stroke Risk in Sickle Cell Disease: A Retrospective Comparative Analysis.

Sickle cell disease (SCD) increases the incidence of childhood stroke eighty-fold. Stroke risk can be estimated by measurement of the blood velocity through the middle cerebral artery (MCA) using transcranial doppler ultrasound (TCD). A high MCA blood velocity indicates increased stroke risk due to cerebral vasculopathy, and first-line treatment to prevent primary or recurrent strokes in high-risk children with SCD has classically been chronic blood transfusions.