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Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years

2022· article· en· W4293116610 on OpenAlexaff
Mohsen Saleh Elalfy, Mona Hamdy, Amal El‐Beshlawy, Fatma Soliman Elsayed Ebeid, Mohamed Badr, Julie Kanter, Baba Inusa, Amira Adly, Suzan Williams, Yurdanur Kılınç, David D. Lee, Caroline Fradette, Anna Rozova, Noemi Toiber Temin, Fernando Tricta, Janet L. Kwiatkowski

Bibliographic record

VenueBlood Advances · 2022
Typearticle
Languageen
FieldMedicine
TopicHemoglobinopathies and Related Disorders
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
Fundersnot available
KeywordsDeferiproneMedicineInternal medicineDeferoxamineClinical endpointAdverse effectGastroenterologyAnemiaNeutropeniaDeferasiroxThalassemiaSickle cell anemiaRandomized controlled trialPediatricsSurgeryDiseaseChemotherapy

Abstract

fetched live from OpenAlex

Long-term safety and efficacy data on the iron chelator deferiprone in sickle cell disease (SCD) and other anemias are limited. FIRST-EXT was a 2-year extension study of FIRST (Ferriprox in Patients With Iron Overload in Sickle Cell Disease Trial), a 1-year, randomized noninferiority study of deferiprone vs deferoxamine in these populations. Patients who entered FIRST-EXT continued to receive, or were switched to, deferiprone. Altogether, 134 patients were enrolled in FIRST-EXT (mean age: 16.2 years), with mean (SD) exposure to deferiprone of 2.1 (0.8) years over the 2 studies. The primary end point was safety. Secondary end points were change in liver iron concentration (LIC), cardiac T2∗, serum ferritin (SF), and the proportion of responders (≥20% improvement in efficacy measure). The most common adverse events considered at least possibly related to deferiprone were neutropenia (9.0%) and abdominal pain (7.5%). LIC (mg/g dry weight) decreased over time, with mean (SD) changes from baseline at each time point (year 1, -2.64 [4.64]; year 2, -3.91 [6.38]; year 3, -6.64 [7.72], all P < .0001). Mean SF levels (μg/L) decreased significantly after year 2 (-771, P = .0008) and year 3 (-1016, P = .0420). Responder rates for LIC and SF increased each year (LIC: year 1, 46.5%; year 2, 57.1%; year 3, 66.1%; SF: year 1, 35.2%; year 2, 55.2%; year 3, 70.9%). Cardiac T2∗ remained normal in all patients. In conclusion, long-term therapy with deferiprone was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias. The trial was registered at www.clinicaltrials.gov as #NCT02443545.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.373
Threshold uncertainty score0.315

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.291
Teacher spread0.274 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations25
Published2022
Admission routes1
Has abstractyes

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