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 safet

Interplay of quantum magnetic and potential scattering around Zn or Ni impurity ions in superconducting cuprates

To describe the scattering of superconducting quasiparticles from non-magnetic (Zn) or magnetic (Ni) impurities in optimally doped high T$_c$ cuprates, we propose an effective Anderson model Hamiltonian of a localized electron hybridizing with $d_{x^2-y^2}$-wave BCS type superconducting quasiparticles with an attractive scalar potential at the impurity site. Due to the strong local antiferromagnetic couplings between the original Cu ions and their nearest neighbors, the localized electron in the Ni-doped materials is assumed to be on the impurity sites, while in the Zn-doped materials the localized electron is distributed over the four nearest neighbor sites of the impurities with a dominant $d_{x^2-y^2}$ symmetric form of the wave function. With Ni impurities, two resonant states are formed above the Fermi level in the local density of states at the impurity site, while for Zn impurities a sharp resonant peak below the Fermi level dominates in the local density of states at the Zn site, accompanied by a small and broad resonant state above the Fermi level mainly induced by the potential scattering. In both cases, there are no Kondo screening effects. The local density of states and their spatial distribution at the dominant resonant energy around the substituted impurities are calculated for both cases, and they are in good agreement with the experimental results of scanning tunneling microscopy in Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ with Zn or Ni impurities, respectively.Comment: 24 pages, Revtex, 8 figures, submitted to Physical Review B for publication. Sub-ject Class: Superconductivity; Strongly Correlated Electron

Quantum computing implementations with neutral particles

We review quantum information processing with cold neutral particles, that is, atoms or polar molecules. First, we analyze the best suited degrees of freedom of these particles for storing quantum information, and then we discuss both single- and two-qubit gate implementations. We focus our discussion mainly on collisional quantum gates, which are best suited for atom-chip-like devices, as well as on gate proposals conceived for optical lattices. Additionally, we analyze schemes both for cold atoms confined in optical cavities and hybrid approaches to entanglement generation, and we show how optimal control theory might be a powerful tool to enhance the speed up of the gate operations as well as to achieve high fidelities required for fault tolerant quantum computation.Comment: 19 pages, 12 figures; From the issue entitled "Special Issue on Neutral Particles

A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

BACKGROUND The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. AIM We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. METHODS Using a bilingual questionnaire (in Malay and English language), we asked our respondents about their attitudes towards allowing family presence (FP) as well as their actual experience of requests from families to be allowed to witness resuscitations. Multiple logistic regression was used to analyze the association between the many variables and a positive attitude towards FP. RESULTS Out of 300 health care professionals who received forms, 270 responded (a 90% response rate). Generally only 15.8% of our respondents agreed to allow relatives to witness resuscitations, although more than twice the number (38.5%) agreed that relatives do have a right to be around during resuscitation. Health care providers are significantly more likely to allow FP if the procedures are perceived as likely to be successful (e.g., intravenous cannulation and blood taking as compared to chest tube insertion). Doctors were more than twice as likely as paramedics to agree to FP (p-value = 0.002). This is probably due to the Malaysian work culture in our health care systems in which paramedics usually adopt a 'follow-the-leader' attitude in their daily practice. CONCLUSION The concept of allowing FP is not well accepted among our Malaysian health care providers