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Integrated safety across six clinical trials of alpha-1 augmentation therapy

2014· article· en· W2154630783 on OpenAlexaff
Robert A. Sandhaus, Kenneth R. Chapman, Jonathan Burdon, Eeva Piitulainen, Niels Seersholm, James Stocks, Jonathan M. Edelman, Martin Bexon, Liping Huang, Noel G. McElvaney

Bibliographic record

VenueEuropean Respiratory Journal · 2014
Typearticle
Languageen
FieldMedicine
TopicInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsMedicineAdverse effectPlaceboInternal medicineClinical trialGastroenterologyIncidence (geometry)SurgeryPathology

Abstract

fetched live from OpenAlex

Background Augmentation therapy with alpha-1 proteinase inhibitor (A 1 -PI) slows emphysema progression in A 1 -PI-deficient patients. Aim This integrated safety summary assessed rates of adverse events (AEs) across six clinical studies of intravenous A 1 -PI Z (Zemaira®, CSL Behring). Methods The data set includes RAPID ( NCT00261833 ), the single largest clinical trial of A 1 -PI augmentation therapy, its ongoing extension study ( NCT00670007 ), and four smaller trials. Results Overall, the incidence of AEs with A 1 -PI Z was not higher than with placebo; most AEs were linked to patients' respiratory conditions. The most common related AEs were headache and dizziness. Six patients died during the studies; none was considered treatment-related. There were five serious AEs judged by the investigators to be at least possibly related to A 1 -PI Z (enterocolitis, pancreatitis, 'adverse drug reaction', back pain, pulmonary fibrosis) and one with placebo (musculoskeletal chest pain). There was no A 1 -PI antibody formation or viral transmission. Safety across six clinical studies of A1-PI therapy A1-PI Z (N=221, SY=426.9, NI=20899) Placebo (N=87, SY=149.1, NI=7276) A1-PI P (Prolastin®; N=32, SY=3.7, NI=160) Events Incidence Per Infusion Events Incidence Per Infusion Events Incidence Per Infusion Any AE 2709 0.1296 1071 0.1472 87 0.5438 At least possibly related AE 124 0.0059 53 0.0073 6 0.0375 SAE* 68 0.0033 21 0.0029 4 0.0250 At least possibly related SAE 5 0.0002 1 0.0001 0 0 N=subjects per group; SY=subject years; NI=number of infusions; AE=adverse events; SAE=serious AE; *At least possibly related or occurring during/within 72 h after infusion Conclusions The AE profile of highly purified A 1 -PI Z is similar to placebo.

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)0.065
metaresearch head score (Gemma)0.073
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.065
Threshold uncertainty score0.343

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0650.073
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0040.006
Bibliometrics0.0020.003
Science and technology studies0.0010.001
Scholarly communication0.0030.002
Open science0.0010.002
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0040.001

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 head0.136
GPT teacher head0.433
Teacher spread0.296 · 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 designMeta-analysis
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

Citations3
Published2014
Admission routes1
Has abstractyes

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