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Record W4280584569 · doi:10.1136/jnnp-2022-329024

Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial

2022· article· en· W4280584569 on OpenAlexfundno aff
Sabrina Paganoni, Suzanne Hendrix, Samuel P. Dickson, Newman Knowlton, James D. Berry, Michael A. Elliott, Samuel Maiser, Chafic Karam, James B. Caress, Margaret Owegi, Adam Quick, James Wymer, Stephen A. Goutman, Daragh Heitzman, Terry Heiman‐Patterson, Carlayne E. Jackson, Colin Quinn, Jeffrey D. Rothstein, Edward J. Kasarskis, Jonathan Katz, Liberty Jenkins, Shafeeq Ladha, Timothy M. Miller, Stephen N. Scelsa, Tuan Vu, Christina Fournier, Kristin Johnson, Andrea Swenson, Namita Goyal, Gary L. Pattee, Suma Babu, Marianne Chase, Derek D’Agostino, Meghan Hall, Gale Kittle, Mathew Eydinov, Joseph Ostrow, Lindsay Pothier, Rebecca Randall, Jeremy M. Shefner, Alexander Sherman, Eric Tustison, Prasha Vigneswaran, Hong Yu, Joshua Cohen, Justin Klee, Rudolph E. Tanzi, Walter Gilbert, Patrick Yeramian, Merit Cudkowicz

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2022
Typearticle
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsnot available
FundersRobert Packard Center for ALS Research, Johns Hopkins UniversityNational Center for Advancing Translational SciencesNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeCytokineticsAcorda TherapeuticsSanofi GenzymeRare Diseases Clinical Research NetworkWeill Cornell Medical CollegeCSL BehringNortheast Amytrophic Lateral Sclerosis ConsortiumIonis PharmaceuticalsSarepta TherapeuticsTarget ALSNational Institutes of HealthRegeneron PharmaceuticalsApellis PharmaceuticalsAlexion PharmaceuticalsALS Hope FoundationAmerican Academy of NeurologyAstraZenecaCongressionally Directed Medical Research ProgramsDisarm TherapeuticsU.S. Department of DefenseSanofiMuscular Dystrophy AssociationHope FoundationUCB PharmaArgenxALS AssociationChan Zuckerberg InitiativeYork UniversityBiogenGlaxoSmithKlineAlnylam Pharmaceuticals
KeywordsAmyotrophic lateral sclerosisMedicinePhenylbutyrateRandomized controlled trialInternal medicineDisease

Abstract

fetched live from OpenAlex

BACKGROUND: Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS). OBJECTIVE: Determine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial. METHODS: Adults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/ TURSO or placebo for 6 months. Those completing randomised treatment could enrol in an open-label extension (OLE) phase and receive PB/TURSO for ≤30 months. Times to the following individual or combined key events were compared in the originally randomised treatment groups over a period spanning trial start through July 2020 (longest postrandomisation follow-up, 35 months): death, tracheostomy, permanent assisted ventilation (PAV) and first hospitalisation. RESULTS: Risk of any key event was 47% lower in those originally randomised to PB/TURSO (n=87) versus placebo (n=48, 71% of whom received delayed-start PB/TURSO in the OLE phase) (HR=0.53; 95% CI 0.35 to 0.81; p=0.003). Risks of death or tracheostomy/PAV (HR=0.51; 95% CI 0.32 to 0.84; p=0.007) and first hospitalisation (HR=0.56; 95% CI 0.34 to 0.95; p=0.03) were also decreased in those originally randomised to PB/TURSO. CONCLUSIONS: Early PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS. TRIAL REGISTRATION NUMBER: NCT03127514; NCT03488524.

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)0.003
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.236
Threshold uncertainty score0.965

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.002
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 head0.025
GPT teacher head0.279
Teacher spread0.253 · 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

Citations66
Published2022
Admission routes1
Has abstractyes

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