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Record W4311024711 · doi:10.1056/nejmoa2209254

Trial of Deferiprone in Parkinson’s Disease

2022· article· en· W4311024711 on OpenAlexaff
David Devos, Julien Labreuche, Olivier Rascol, Jean‐Christophe Corvol, Alain Duhamel, Pauline Guyon Delannoy, Werner Poewe, Yaroslau Compta, Nicola Pavese, Evžen Růžička, Petr Dušek, Bart Post, Bastiaan R. Bloem, Daniela Berg, Walter Maetzler, Markus Otto, Marie‐Odile Habert, Stéphane Lehéricy, Joaquim J. Ferreira, Richard Dodel, Christine Tranchant, Alexandre Eusébio, Stéphane Thobois, Ana Marquès, Wassilios G. Meissner, Fabienne Ory‐Magne, Uwe Walter, Rob M.A. de Bie, Miguel Gago, Dolores Vilas, Jaime Kulisevsky, Cristina Januário, Miguel Vilhena Soares Coelho, Stefanie Behnke, Paul Worth, Klaus Seppi, Thavarak Ouk, Camille Potey, Céline C. Leclercq, Romain Viard, Grégory Kuchcinski, Renaud Lopes, Jean‐Pierre Pruvo, Pascal Pigny, Guillaume Garçon, O. Simonin, Jessica Carpentier, Anne‐Sophie Rolland, Dag Nyholm, Christoph Scherfler, Jean‐François Mangin, Marie Chupin, Régis Bordet, David T. Dexter, Caroline Fradette, Michael Spino, Fernando Tricta, Scott Ayton, Ashley I. Bush, Jean-Christophe Devedjian, James A. Duce, Ioav Cabantchik, Luc Defebvre, Dominique Deplanque, Caroline Moreau

Bibliographic record

VenueNew England Journal of Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsUniversity of Toronto
FundersInserm TransfertMedical Research CouncilCentre hospitalier régional universitaire de LilleInstitut National de la Santé et de la Recherche Médicale
KeywordsDeferiproneParkinson's diseaseMedicineDiseaseInternal medicineThalassemia

Abstract

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BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.025
GPT teacher head0.283
Teacher spread0.258 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
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

Citations223
Published2022
Admission routes1
Has abstractyes

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