Physicians' Perception of Sickle-cell Disease Pain.

The aim of this study was to evaluate the physician's perception of pain experienced by patients with sickle-cell disease (SCD). Pain experiences reported by patients were compared with physicians' perception of the patient's pain, and the treatment decision-making process was evaluated. Fifty-two patient-physician pairs were assessed. Before the clinic visit, the patients completed a 3-item on pain experienced 24 h prior to the visit and the PHQ-9. After the patient visit, the physicians completed a questionnaire assessing their perception of the patient's pain and a questionnaire on the factors taken into consideration when evaluating the patient's pain experience. The physicians rated the patients' pain as more intense than did the patients themselves; and there was agreement between pain intensity measurements (p < 0.05). The physicians' perception was influenced by the pain intensity reported by the patient, results of blood count at the time of the patient visit, and medication availability in the public health services. However, these factors were not predictive of the patient's pain intensity perceived by the physician. Patients' depressive symptoms were not predictive factor of the physicians' perception. Biochemical, genetic and symptomatic characteristics of SCD influenced the physicians' perception of the patient's pain experience, while psychosocial aspects did not.

A double-blind, placebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease.

This placebo-controlled phase II study evaluated the pharmacodynamics, efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), a fetal globin gene-inducing short-chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48 weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years (range: 12-55 years) and 37 subjects (49%) were treated previously with hydroxycarbamide. Sixty subjects (79%) had Hb SS and 16 (21%) had S/ß(0) thalassemia. The study was terminated after a planned interim analysis showed no significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises in the HQK-1001 group. For 54 subjects with Week 24 data, the mean absolute increase in Hb F was 0.9% (95% confidence interval (CI): 0.1-1.6%) with HQK-1001 and 0.2% (95% CI: -0.7-1.1%) with placebo. Absolute increases in Hb F greater than 3% were noted in 9 of 38 subjects (24%) administered HQK-1001 and 1 of 38 subjects (3%) administered placebo. The mean changes in hemoglobin at Week 24 were comparable between the two groups. The mean annualized rate of pain crises was 3.5 with HQK-1001 and 1.7 with placebo. The most common adverse events in the HQK-1001 group, usually graded as mild or moderate, consisted of nausea, headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK-1001 at this dose and schedule are not recommended in SCD. Intermittent HQK-1001 administration, rather than a daily regimen, may be better tolerated and more effective, as shown previously with arginine butyrate, and warrants further evaluation.