Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study

<p>BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P).</p><p>PATIENTS AND METHODS: Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study.</p><p>RESULTS: Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08-2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004).</p><p>CONCLUSIONS: QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.</p>

Investigation of the effects of flow conditions at rotor inlet on mixed flow turbine performance for automotive applications

Current trends in the automotive industry have placed increased importance on engine downsizing for passenger vehicles. Engine downsizing often results in reduced power output and turbochargers have been relied upon to restore the power output and maintain drivability. As improved power output is required across a wide range of engine operating conditions, it is necessary for the turbocharger to operate effectively at both design and off-design conditions. One off-design condition of considerable importance for turbocharger turbines is low velocity ratio operation, which refers to the combination of high exhaust gas velocity and low turbine rotational speed. Conventional radial flow turbines are constrained to achieve peak efficiency at the relatively high velocity ratio of 0.7, due the requirement to maintain a zero inlet blade angle for structural reasons. Several methods exist to potentially shift turbine peak efficiency to lower velocity ratios. One method is to utilize a mixed flow turbine as an alternative to a radial flow turbine. In addition to radial and circumferential components, the flow entering a mixed flow turbine also has an axial component. This allows the flow to experience a non-zero inlet blade angle, potentially shifting peak efficiency to a lower velocity ratio when compared to an equivalent radial flow turbine.<br/>This study examined the effects of varying the flow conditions at the inlet to a mixed flow turbine and evaluated the subsequent impact on performance. The primary parameters examined were average inlet flow angle, the spanwise distribution of flow angle across the inlet and inlet flow cone angle. The results have indicated that the inlet flow angle significantly influenced the degree of reaction across the rotor and the turbine efficiency. The rotor studied was a custom in-house design based on a state-of-the-art radial flow turbine design. A numerical approach was used as the basis for this investigation and the numerical model has been validated against experimental data obtained from the cold flow turbine test rig at Queen’s University Belfast. The results of the study have provided a useful insight into how the flow conditions at rotor inlet influence the performance of a mixed flow turbine.

Complexity of risk: Mixed methods approach to understanding youth risk and insecurity in post-conflict settings

In settings of intergroup conflict, identifying contextually-relevant risk factors for youth development in an important task. In Vukovar, Croatia, a city devastated during the war in former Yugoslavia, ethno-political tensions remain. The current study utilized a mixed method approach to identify two salient community-level risk factors (ethnic tension and general antisocial behavior) and related emotional insecurity responses (ethnic and non-ethnic insecurity) among youth in Vukovar. In Study 1, focus group discussions (N=66) with mother, fathers, and adolescents 11 to 15-years-old were analyzed using the Constant Comparative Method, revealing two types of risk and insecurity responses. In Study 2, youth (N=227, 58% male, M=15.88 SD=1.12 years old) responded to quantitative scales developed from the focus groups; discriminate validity was demonstrated and path analyses established predictive validity between each type of risk and insecurity. First, community ethnic tension (i.e., threats related to war/ethnic identity) significantly predicted ethnic insecurity for all youth (β=.41, p&lt;.001). Second, experience with community antisocial behavior (i.e., general crime found in any context) predicted non-ethnic community insecurity for girls (β=.32, p&lt;.05), but not for boys. These findings are the first to show multiple forms of emotional insecurity at the community level; implications for future research are discussed.