Comparison of weekly and daily recall of pain as an endpoint in a randomized phase 3 trial of cabozantinib for metastatic castration-resistant prostate cancer

Introduction: Scant evidence reveals whether the use of weekly versus daily pain ratings leads to meaningful differences when measuring pain as a clinical trial outcome. We compared the ability of weekly ratings and descriptors of daily ratings to evaluate pain as an endpoint in a randomized phase 3 drug trial. Methods: Participants (n = 119) with metastatic castration-resistant prostate cancer were randomized to treatment arms and rated their pain on the average and at its worst during a baseline week and at weeks 3, 6, and 12 of study treatment. For each reporting period, participants rated their pain daily for 7 days. On day 7, participants rated their pain over the prior 7 days. We estimated mean differences and intraclass correlation coefficients of the weekly ratings and the mean and the maximum daily ratings. We compared the ability of the weekly ratings and the daily rating descriptors to detect change in pain and evaluated the agreement of the weekly rating and the mean daily rating of pain at its worst to detect treatment response. Results: For both pain constructs, the weekly rating was consistently higher than the mean daily rating and lower than the maximum daily rating yet was moderately to highly correlated with both daily rating descriptors (intraclass correlation coefficient range = 0.55–0.94). The weekly rating and the daily rating descriptors consistently detected change in pain for the study sample and participant subgroups. Substantial agreement existed between the weekly rating and the mean daily rating of pain at its worst when used with trial protocol opioid criteria to detect treatment response (Cohen’s κ = 0.71). Conclusion: Use of daily over weekly ratings delivered no added benefit in evaluating pain in this clinical trial. This study is the first to compare weekly and daily recall to measure pain as an endpoint in a randomized phase 3 drug trial, and the pattern of differences in ratings that we observed is consistent with other recent evaluations of weekly and daily symptom reporting

Role of Fragment Higher Static Deformations in the Cold Binary Fission of 252^{252}Cf

We study the binary cold fission of $^{252}$Cf in the frame of a cluster model where the fragments are born to their respective ground states and interact via a double-folded potential with deformation effects taken into account up to multipolarity $\lambda=4$. The preformation factors were neglected. In the case when the fragments are assumed to be spherical or with ground state quadrupole deformation, the $Q$-value principle dictates the occurence of a narrow region around the double magic $^{132}$Sn, like in the case of cluster radioactivity. When the hexadecupole deformation is turned on, an entire mass-region of cold fission in the range 138 - 156 for the heavy fragment arise, in agreement with the experimental observations. This fact suggests that in the above mentioned mass-region, contrary to the usual cluster radioactivity where the daughter nucleus is always a neutron/proton (or both) closed shell or nearly closed shell spherical nucleus, the clusterization mechanism seems to be strongly influenced by the hexadecupole deformations rather than the $Q$-value.Comment: 10 pages, 12 figure

Catching Element Formation In The Act ; The Case for a New MeV Gamma-Ray Mission: Radionuclide Astronomy in the 2020s

High Energy Astrophysic