Long-term treprostinil in pulmonary arterial hypertension: is the glass half full or half empty?
Bibliographic record
Abstract
Pulmonary arterial hypertension (PAH) has traditionally been considered as an inevitably fatal disease. In the 1980s, a national registry funded by the National Institutes of Health (NIH) described the natural history of idiopathic PAH 1. The median survival was <3 yrs and prognosis was mostly related to baseline functional capacity and pulmonary haemodynamics. In case series, the long-term outcome of patients with PAH associated with connective tissue disease, portal hypertension and HIV infection appeared to be even worse 2. This was before the era of PAH-specific therapies. In the last decade, significant advances in the current understanding of the disease have led to the development of new specific treatments. In 1996, a placebo-controlled trial demonstrated significant survival benefit with i.v. epoprostenol in idiopathic PAH patients 3. Several other therapies, including prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors, were subsequently evaluated in short-term randomised placebo-controlled trials. These studies demonstrated improvements in pulmonary haemodynamics, exercise capacity and quality of life 4–6. This new era of therapy has clearly brought enthusiasm among physicians. From a clinician's perspective, the glass has been half filled. Treprostinil s.c. was evaluated in a large randomised placebo-controlled trial involving 470 PAH patients randomised to either s.c. treprostinil or placebo 7. Over a 12-week period, s.c. treprostinil improved patients’ exercise capacity, PAH-related symptoms and haemodynamics. The median placebo-corrected increase in 6-min walking distance was 16 m, with greater improvements in severely ill patients at baseline and in those who could tolerate the highest doses. Unfortunately, this short-term trial, as with others, was underpowered and not designed to detect survival benefit. Indeed, the most ill patients are no longer entered into placebo-controlled …
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| 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".