Real World Analysis of Symptoms, Diagnostic Patterns, and Provider Perspective on Acute Hepatic Porphyrias
Bibliographic record
Abstract
Introduction: Acute hepatic porphyrias (AHPs) are rare genetic diseases caused by mutations of enzymes involved in hepatic heme synthesis. Neurotoxic heme intermediates, aminolevulinic acid (ALA) and porphobilinogen (PBG), accumulate and can cause potentially life-threatening attacks and chronic symptoms. The study objective was to understand physician experiences diagnosing AHPs and to characterize the AHP patient population in a real-world setting. Methods: Physicians (n=175) from the US (29%), EU-5 (57%), Canada (9%), and Japan (6%) who actively managed or treated AHP patients (with and without recurrent attacks) in the year prior were recruited from 9/2017-10/2017 to complete an online survey collecting information on demographics, familiarity with AHPs and diagnostic tests, perspective on symptoms important to diagnosis, referral patterns, and treatment preferences. Subsequently, physicians reviewed 1-4 of their AHP patients' charts (n=546; 32% US), sharing data on anonymized patient demographics, medical history, number of porphyria attacks, and symptoms. Results: Physicians had a mean of 18 years of experience, 51% worked in academic settings, and the most common specialty was gastroenterology (25%). Symptoms considered informative for AHP diagnosis included abdominal pain (88%), red/dark urine (75%), muscle weakness (63%), vomiting (62%), fatigue (59%), and nausea (57%). AHP diagnostic tests considered informative included ALA in urine (73%) and PBG in urine (68%); however, other nonspecific tests were also commonly considered informative. Among charts reviewed, patients' mean age was 40 years, 53% were female, and 82% had acute intermittent porphyria (AIP). Initially, 26% of AHPs were misdiagnosed and 31% were diagnosed correctly (43% did not know this information). Most common misdiagnoses were nonspecific abdominal pain (32%), irritable bowel syndrome (27%), depression (25%), and fibromyalgia (25%). Patients had a mean of 1.8 attacks and 1.1 hospitalizations in the past year. Most common chronic symptoms reported between attacks were abdominal pain (50%), fatigue (36%), and nausea (32%). Conclusion: This research revealed there may be underdiagnoses or misdiagnoses due to common symptomology associated with AHPs and/or lack of understanding of appropriate laboratory and genetic testing procedures. Among patients diagnosed with AHPs, both acute attacks as well as chronic symptoms were reported indicating AHPs have both acute and chronic manifestations.
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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 | 0.002 | 0.013 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
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".