Bleeding before prophylaxis in severe hemophilia: paradigm shift over two decades
Bibliographic record
Abstract
Bleeding before prophylaxis in severe hemophilia: paradigm shift over two decades Prophylaxis for hemophilia is the scheduled infusion of the missing clotting factor with pre-specified dose, with the intention of preventing bleeds and subsequent hemophilic arthropathy.It is the treatment of choice for patients with severe hemophilia A in countries with available resources. 1 Around the year 2000 it was reported that prophylaxis is most efficient when initiated early: before 3 years of age 2 or directly after the first joint bleed.3,4 These strategies are reflected in the two most frequently used definitions of primary prophylaxis.The European Pediatric Network for Hemophilia Management (PedNet) first specified primary prophylaxis as starting before two years of age OR before the second joint bleed, 5 and The World Federation of Hemophilia (WFH) as starting before the age of three years AND before the second joint bleed, in the documented absence of osteochondral joint disease. 1 Early prophylaxis may require placing a central venous access device (CVAD) to facilitate frequent venous access, but these devices carry a risk of infections and thrombotic complications.6 In an attempt to reduce the need for CVADs while initiating early prophylaxis, Petrini and colleagues started prophylaxis with once-weekly infusions; 2,7 many authors have subsequently published or recommended protocols starting with once-weekly infusions.[8][9][10] The present study assesses how the increasing awareness of the importance of early prophylaxis affected bleeding before prophylaxis, CVAD use, initial prophylactic regimens, and achievement of primary prophylaxis.Data on 919 patients with severe hemophilia A (FVIII<0.01IU/mL), born 1990-2010, collected for the CANAL study 11 (n=313) and the PedNet registry 12 (n= 606) were used.Nine and 16 patients were excluded from CANAL and PedNet, respectively, because no treatment data were available.Case report forms and inclusion and exclusion criteria were the same for both datasets.11,12 Anonymized data on patients' demographics, bleeding, and details on all factor administrations were collected by the participating centers until 1 st May 2013.For the present analysis, patients were followed from birth until the 50 th treatment day with FVIII or the development of a clinically relevant inhibitor, defined as at least two positive inhibitor titers, combined with a decreased in vivo Factor VIII recovery.Start of prophylaxis was defined as the regular infusion of FVIII at least
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.018 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.014 | 0.018 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".