In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) ...versus placebo (11.4 versus 5.5 months; HR, 0.42; P < 0.001). Here, we present PFS using retrospective blinded independent central review (BICR) and final median overall survival (OS), including an assessment highlighting the impact of patient crossover from placebo to sunitinib.
In this randomized, double-blind, placebo-controlled study, cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a two-reader, two-time-point lock, followed by a sequential locked-read, batch-mode paradigm. OS was summarized using the Kaplan–Meier method and Cox proportional hazards model. Crossover-adjusted OS effect was derived using rank-preserving structural failure time (RPSFT) analyses.
Of 171 randomized patients (sunitinib, n = 86; placebo, n = 85), 160 (94%) had complete scan sets/time points. By BICR, median (95% confidence interval CI) PFS was 12.6 (11.1–20.6) months for sunitinib and 5.8 (3.8–7.2) months for placebo (HR, 0.32; 95% CI 0.18–0.55; P = 0.000015). Five years after study closure, median (95% CI) OS was 38.6 (25.6–56.4) months for sunitinib and 29.1 (16.4–36.8) months for placebo (HR, 0.73; 95% CI 0.50–1.06; P = 0.094), with 69% of placebo patients having crossed over to sunitinib. RPSFT analysis confirmed an OS benefit for sunitinib.
BICR confirmed the doubling of PFS with sunitinib compared with placebo. Although the observed median OS improved by nearly 10 months, the effect estimate did not reach statistical significance, potentially due to crossover from placebo to sunitinib.
NCT00428597.
To evaluate non-compliance with osteoporosis medications as well as its implications for health and economic outcomes in actual practice.
Data on demographics, prescription drug dispensing, physician ...services and hospitalizations were obtained from a US managed care database for women with osteoporosis who were dispensed an osteoporosis medication between 1997 and 2002.
Each subject's pattern of osteoporosis medication use was reconstructed using dispensing records. Subjects were considered compliant over a given period if their medication possession ratio (MPR) was ≥80% and gradients of compliance (<50% poor, 50–80% medium, 80–90% good, >90% excellent) were also examined. Using proportional hazards, the association between compliance over time and fracture rates was examined; Poisson regression was used for hospitalization and log-linear regression for medical costs.
38,120 women with osteoporosis were identified with a mean age of 66 years and an average follow-up of 1.7 years. Three quarters of them had an MPR below 80% when their entire follow-up was considered. Low compliance was associated with a 17% (95% CI 9–25%) increase in the fracture rate, adjusting for other known risk factors. Controlling for the specific drug regimen did not alter the association. Low compliance was also associated with a 37% (95% CI 32–43%) increase in the risk of all-cause hospitalization; and average monthly costs for all medical services combined were higher: $600 vs. $340 (
P < 0.0001). Similar associations were observed when using the gradients of compliance.
The desired goal of keeping patients with osteoporosis on chronic treatment is not being achieved adequately in actual practice and the potential social and economic implications of this behavior are substantial. Until compliance is improved, society will continue to fail in meeting an important public health goal.
The decomposition and nutrient release temporal patterns of three oil palm residues used as soil mulch were studied. Empty fruit bunches (EFB; 1000 kg plot⁻¹), Eco‐mat (processed EFB carpet; 30 kg ...plot⁻¹), and pruned palm fronds (180 kg plot⁻¹) were left to decompose (and sampled monthly) on the soil surface for 8 months. The frond's leaflets had the highest initial concentration for most nutrients, and the frond's rachis and Eco‐mat the lowest. The order of residue quality and rate of residue mass loss were: leaflets > fronds > EFB > Eco‐mat > rachis. EFB however had a higher mass loss rate than the fronds. Residue mass loss and nutrient release rates were faster at the beginning than at the end of the decomposition period. Leaflets released the highest total amount of nutrients (except for K), and rachis the lowest. The fronds released either significantly higher (for N and Ca) or not significantly different (for P and Mg) total amount of nutrients than EFB. Converting EFB into Eco‐mat had resulted in nutrient losses (e.g. N, K and Mg) and a residue quality reduction in Eco‐mat. This study's results would aid in better soil and oil palm fertilisation management.
This study is carried out to scrutinize the Hiemenz flow for ternary hybrid nanofluid flow across a stretching/shrinking sheet. This study aims to inspect the impacts of variations in the ...stretching/shrinking parameter and the volume fraction of nanoparticles on key aspects of the ternary hybrid nanofluid flow, specifically the skin friction, Nusselt number (which relates to heat transfer), velocity profiles, and the temperature profiles. The flow equations transform into a system of ordinary differential equations (ODEs) using a similarity transformation. Subsequently, the system is numerically solved using the MATLAB software’s 4th-order accuracy boundary value problem solver, known as “bvp4c”. Numeric findings reveal that skin friction values exhibit variations based on the magnitude of the stretching/shrinking parameter. Moreover, in the specific context of the flow problem being studied, the heat conduction efficiency of the hybrid (ternary) nanofluid surpasses that of the hybrid nanofluid. The system yields two distinct solutions within a specific shrinking/stretching parameter interval. Through an examination of the temporal stability of the solutions, it was determined that only one remained stable over an extended period. Remember that these current findings hold solely for the combination of copper, alumina, and titania.
Clinical trials have demonstrated that drug therapy can reduce osteoporosis-related fracture risk in women over 50 years of age. Noncompliance could considerably limit the effectiveness observed in ...actual practice, however. The objective of this study was therefore to estimate fracture risk in relation to compliance with osteoporosis medication in actual practice.
Demographic, prescription drug use, physician services, and hospitalization information for women with osteoporosis who were dispensed an osteoporosis medication between 1996 and 2001 was obtained from the Saskatchewan health data files. Compliance to treatment was defined as drug available to cover 80% of the time. Subsequent fractures were identified via hospitalizations or physician contacts with a relevant diagnostic or procedure code. The risk of fractures in relation to compliance was examined using a Cox proportional hazards model with time-dependent covariates. The impact of other patient characteristics, including age, having suffered a prior fracture, and prior use of osteoporosis medication and steroids, was also examined.
11,249 women suffering from osteoporosis were identified with a mean age at the time of the index prescription of 68.4 years and average follow-up of 2 years. The overall fracture rate was 4.5% per year. Patients who complied experienced a 16% lower fracture rate. This association was maintained within subgroups and after controlling for other patient characteristics that independently predict the fracture rate.
These results indicate that improving compliance in actual practice may significantly decrease osteoporosis-related fracture risk.
The idea of this work is to explore the impact of endothermic and exothermic chemical reactions on time-dependent magnetohydrodynamic nanomaterial flow, heat and mass transfer characteristics induced ...by a rotating sphere. Implementing combined influence of chemical reaction and activation energy is vital for improving the efficiency of thermal transmission processes in different industrial applications including energy production, pollutant control system, material processing, etc. Owing to its usage, this investigation aims to examine the influence of endothermic, exothermic reactions and activation energy on the flow of Magnetohydrodynamic over a rotating sphere with the nanoparticles that contains a mixture of water and titanium oxide. Furthermore, this investigation studies the influence of activation energy on both heat and mass transfer in fluid systems. The objective is to boost our insight into difficult problems, which could have real-world usages in areas including combustion engines. The PDEs were transformed into ODE via applying similarity variables and then solved using the BVP4c technique. This study shows that the fluid temperature reduces the reaction rate and improves the activation energy for an exothermic reaction. Also, in the case of an endothermic reaction, the fluid temperature increases the reaction rate and reduces the activation energy. Further, in exothermic reactions, the heat distribution rate is higher than endothermic reactions, considering activation energy and solid volume fraction while the mass transfer rate declines for improved values of these two factors.
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