Bibliographic record
Abstract
Background and aims: Acute Hepatic Porphyrias (AHPs) are rare, genetic diseases caused by mutations in the heme pathway.Central to AHPs is the upregulation of aminolevulinic acid synthase1 (ALAS1), the first, rate-limiting enzyme which causes accumulation of neurotoxic heme intermediates, aminolevulinic acid (ALA) and porphobilinogen (PBG).This results in life-threatening attacks and chronic, debilitating manifestations due to injury to the nervous systems, including neurovisceral pain, fatigue, and motor weakness.Methods: EXPLORE is the first observational study characterizing clinical management of patients with AHPs with ≥3 attacks/year, including patients receiving prophylactic treatment to prevent attacks.We will be presenting updated ≥12 month data.Results: 112 patients enrolled from 13 countries.Patients reported a mean of 9.3 attacks in 12 months prior to the study, with pain (99%), mood/sleep, and digestive (each 96%) symptoms being the most common.Annualized attack rate on study was 4.9 attacks/person, of which 77% required treatment.For those on hemin prophylactically, mean attack rate/person-year=4.0.Chronic symptoms were reported by 65% of patients, with pain (63%), mood/sleep (44%), and digestive (36%) manifestations most frequent.The EQ5D quality of life score was 66 (1-100); 35% had some difficulty walking and 57% had difficulty with usual activities or anxiety/depression.Mean ALA and PBG levels at screening (during non-attack) were increased to 8Xs and 20Xs ULN, respectively.Conclusion: EXPLORE demonstrates that patients suffer from chronic symptoms in addition to frequent attacks that decrease quality of life.Given morbidity and mortality, there remains an unmet need for novel therapies to prevent attacks and treat chronic symptoms.
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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 | 0.001 | 0.003 |
| 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 | 0.000 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.002 | 0.004 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.894 | 0.783 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".