Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial

Background: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.

Objective: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.

Design, setting, and participants: Nine hundred and twenty one patients enrolled at 136 centers globally.

Intervention: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.

Outcome measurements and statistical analysis: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.

Results and limitations: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0–1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2–3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.52–0.93; p = 0.013) and opioid (HR = 0.68; 95% CI: 0.54–0.86; p = 0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR = 0.56, 95% CI: 0.39–0.82, p = 0.002; opioid subgroup: HR = 0.72, 95% CI: 0.53–0.98, p = 0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR = 0.62, 95% CI: 0.46–0.85,p = 0.002). Adverse event incidences were similar between opioid subgroups.

Conclusions: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.

Patient summary: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.

An Assessment of Psychological Need in Emergency Medical Staff in the Northern Health and Social Care Trust Area

Setting: Psychological stress is increasingly recognised within emergency medicine, given the environmental and clinical stressors associated with the specialism. The current study assessed whether psychological distress is experienced by emergency medical staff and if so, what is the expressed need within this population? Participants: Participants included ambulance personnel, nursing staff, doctors and ancillary support staff within two Accident and Emergency (A&E) departments and twelve ambulance bases within one Trust locality in NI (N = 107). Primary and secondary outcome measures: The General Health Questionnaire (GHQ-12, Goldberg, 1972, 1978), Secondary Traumatic Stress Scale (STSS, Bride, 2004) and an assessment of need questionnaire were completed and explored using mixed method analysis. Results: Results showed elevated levels of psychological distress within each profession except ambulance service clinical support officers (CSOs). Elevated levels of secondary trauma symptomatology were also found; the highest were within some nursing grades and junior doctors. Decreased enjoyment in job over time was significantly associated with higher scores. Analysis of qualitative data identified sources of stress to include low morale. A total of 65% of participants thought that work related stressors had negatively affected their mental health. Participants explored what they felt could decrease psychological distress including improved resources and psychoeducation. Conclusion: There were elevated levels of distress and secondary traumatic stress within this population as well as an expressed level of need, on both systemic and support levels.

Design and Implementation of a Low Cost Virtual Rugby Decision Making Interactive

The paper describes the design and implementation of a novel low cost virtual rugby decision making interactive for use in a visitor centre. Original laboratory-based experimental work in decision making in rugby, using a virtual reality headset [1] is adapted for use in a public visitor centre, with consideration given to usability, costs, practicality and health and safety. Movement of professional rugby players was captured and animated within a virtually recreated stadium. Users then interact with these virtual representations via use of a lowcost sensor (Microsoft Kinect) to attempt to block them. Retaining the principles of perception and action, egocentric viewpoint, immersion, sense of presence, representative design and game design the system delivers an engaging and effective interactive to illustrate the underlying scientific principles of deceptive movement. User testing highlighted the need for usability, system robustness, fair and accurate scoring, appropriate level of difficulty and enjoyment.