Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study.

ABSTRACT: Phase 2a of the PUCCINI study was a placebo-controlled, double-blind, parallel-group, multicenter, proof-of-concept study evaluating the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with diabetic neuropathic pain (DNP) ( ClinicalTrials.gov NCT04641273). Adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain were enrolled and randomized 1:1 to 150 mg oral eliapixant twice daily or placebo for 8 weeks. The primary endpoint was change from baseline in weekly mean 24-hour average pain intensity score at week 8. In total, 135 participants completed treatment, 67 in the eliapixant group and 68 in the placebo group. At week 8, the change from baseline in posterior mean 24-hour average pain intensity score (90% credible interval) in the eliapixant group was -1.56 (-1.95, -1.18) compared with -2.17 (-2.54, -1.80) for the placebo group. The mean treatment difference was 0.60 (0.06, 1.14) in favor of placebo. The use of a model-based framework suggests that various factors may contribute to the placebo-responder profile. Adverse events were mostly mild or moderate in severity and occurred in 51% of the eliapixant group and 48% of the placebo group. As the primary endpoint was not met, the PUCCINI study was terminated after completion of phase 2a and did not proceed to phase 2b. In conclusion, selective P2X3 antagonism in patients with DNP did not translate to any relevant improvement in different pain intensity outcomes compared with placebo. Funding: Bayer AG.

Outcome of aortic valve replacement with bioprostheses in the elderly.

BACKGROUND AND AIM OF THE STUDY: Today, the elderly population continues to increase worldwide, and rates of aortic stenosis (AS) climb with age. Since aortic valve replacement (AVR) is the current treatment for elderly patients with symptomatic AS, the number of patients undergoing AVR is expected to grow. METHODS: Among patients operated on at Helsinki University Hospital between 1992 and 1997, a cohort (n = 145) was followed after AVR with a bioprosthesis. The patients were allocated to three groups, based on their age at the time of surgery: > or = 80 years (n = 30), < 80 to > or = 70 years (n = 94), and < or = 70 years (n = 21). All data relating to preoperative risk factors were collected. A control examination, which included echocardiography, was performed at least five years after surgery, and the follow up was continued until July 2006. The number of deaths and causes of death, as well as valve-related complications, were noted. RESULTS: The 30-day mortality rates were 3.3% in the oldest (> or = 80-year) group, 6.4% in the middle (< 80 to > or = 70-year) group, and zero in the youngest (< or = 70-year) group. The mean age at death was 88 and 81 years in the oldest and middle groups, respectively. In the oldest and youngest groups, there were no reoperations, but five valve-related reoperations were performed during follow up in the middle group. At the control visit, the left ventricular ejection fraction was > 60% in all groups. In the oldest and middle groups the aortic valve gradient was lower than the preoperative level, while the left ventricular diameters and wall dimensions were smaller (p < 0.05). Valve calcification was observed in one patient in the youngest group. CONCLUSION: Elderly patients who had undergone AVR with a bioprosthesis had a good outcome after more than 10 years of follow up, with an improved cardiac function being preserved for at least seven years after surgery. Despite a severely impaired preoperative aortic valve function, octogenarians especially had a good life expectancy, possibly due to their low comorbidity rates. Hence, AVR with a bioprosthesis proved to be an excellent treatment in this patient group.

Evaluation of the clinical association between exfoliation syndrome and abdominal aortic aneurysm.

PURPOSE: To assess the validity of the suggested association between intraocular exfoliation syndrome and aneurysm of the abdominal aorta. METHODS: A total of 77 patients recently operated for abdominal aortic aneurysm underwent biomicroscopy under pupillary dilatation to detect the presence of manifest and suspect deposits of exfoliation material. RESULTS: The mean age of the 71 (92%) male and six female subjects was 73 years (range: 59-88 years). Manifest exfoliation was detected in 11 patients (14%; 95% CI 7-24), five of whom were aged 60-69 years and six of whom were aged 70-79 years. In addition, four patients (5%; 95% CI 1-13) had suspect exfoliation. CONCLUSIONS: The prevalence of exfoliation syndrome in patients operated for abdominal aortic aneurysm was similar to that in the general population of the same age in Finland. This finding does not support the proposed connection between exfoliation syndrome and abdominal aortic aneurysm.