Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits Up to 9 Years of Treatment
Why this work is in the frame
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Bibliographic record
Abstract
Context: Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality. Objective: To determine whether hydroxyurea attenuates mortality in patients with SCA. Design: Long-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients' Follow-up, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period. Setting: Inpatients and outpatients in 21 sickle cell referral centers in the United States and Canada. Patients: Two-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients. Intervention: In the MSH, patients were randomly assigned to receive hydroxyurea (n=152) or placebo (n=147). Main Outcome Measures: Mortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts, The randomized trial was not designed to detect specified differences in mortality. Results: Seventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250000/mm3 and hemoglobin levels lower than 9 g/dL had increased mortality (P=.002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/ dL after the trial was completed compared with 15% when HbF levels were 0.5 g/ dL or higher (P=.03). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P=.02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P=.06). Taking hydroxyurea was associated with a 40% reduction in mortality (P=.04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal. Conclusions: Adult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown.
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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 | 0.000 |
| 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 | 0.000 |
| 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 | 0.000 |
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 it