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.
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 imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
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.
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 teacher head, 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".