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

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).

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.

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).

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.

Does video feedback analysis improve CPR performance in phase 5 medical students?

Background The use of simulation in medical education is increasing, with students taught and assessed using simulated patients and manikins. Medical students at Queen’s University of Belfast are taught advanced life support cardiopulmonary resuscitation as part of the undergraduate curriculum. Teaching and feedback in these skills have been developed in Queen’s University with high-fidelity manikins. This study aimed to evaluate the effectiveness of video compared to verbal feedback in assessment of student cardiopulmonary resuscitation performance Methods Final year students participated in this study using a high-fidelity manikin, in the Clinical Skills Centre, Queen’s University Belfast. Cohort A received verbal feedback only on their performance and cohort B received video feedback only. Video analysis using ‘StudioCode’ software was distributed to students. Each group returned for a second scenario and evaluation 4 weeks later. An assessment tool was created for performance assessment, which included individual skill and global score evaluation. Results One hundred thirty eight final year medical students completed the study. 62 % were female and the mean age was 23.9 years. Students having video feedback had significantly greater improvement in overall scores compared to those receiving verbal feedback (p = 0.006, 95 % CI: 2.8–15.8). Individual skills, including ventilation quality and global score were significantly better with video feedback (p = 0.002 and p < 0.001, respectively) when compared with cohort A. There was a positive change in overall score for cohort B from session one to session two (p < 0.001, 95 % CI: 6.3–15.8) indicating video feedback significantly benefited skill retention. In addition, using video feedback showed a significant improvement in the global score (p < 0.001, 95 % CI: 3.3–7.2) and drug administration timing (p = 0.004, 95 % CI: 0.7–3.8) of cohort B participants, from session one to session two. Conclusions There is increased use of simulation in medicine but a paucity of published data comparing feedback methods in cardiopulmonary resuscitation training. Our study shows the use of video feedback when teaching cardiopulmonary resuscitation is more effective than verbal feedback, and enhances skill retention. This is one of the first studies to demonstrate the benefit of video feedback in cardiopulmonary resuscitation teaching.

Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis

Background

It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients.

Purpose

To evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness.

Methods

We searched Medline, EMBASE and the Cochrane central register of controlled trials from 1980 to June 2016, and manually reviewed relevant conference proceedings from 2009 to the present. Two reviewers independently assessed search results for inclusion and undertook data extraction and quality appraisal. We included randomised trials comparing fluid regimens with differing fluid balances between groups, and observational studies investigating the relationship between fluid balance and clinical outcomes.

Results

Forty-nine studies met the inclusion criteria. Marked clinical heterogeneity was evident. In a meta-analysis of 11 randomised trials (2051 patients) using a random-effects model, we found no significant difference in mortality with conservative or deresuscitative strategies compared with a liberal strategy or usual care [pooled risk ratio (RR) 0.92, 95 % confidence interval (CI) 0.82–1.02, I2 = 0 %]. A conservative or deresuscitative strategy resulted in increased ventilator-free days (mean difference 1.82 days, 95 % CI 0.53–3.10, I2 = 9 %) and reduced length of ICU stay (mean difference −1.88 days, 95 % CI −0.12 to −3.64, I2 = 75 %) compared with a liberal strategy or standard care.

Conclusions

In adults and children with ARDS, sepsis or SIRS, a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care. The effect on mortality remains uncertain. Large randomised trials are needed to determine optimal fluid strategies in critical illness.