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.

Photoionization of Co+ and electron-impact excitation of Co2 + using the Dirac R-matrix method

Modelling of massive stars and supernovae (SNe) plays a crucial role in understanding galaxies. From this modelling we can derive fundamental constraints on stellar evolution, mass-loss processes, mixing, and the products of nucleosynthesis. Proper account must be taken of all important processes that populate and depopulate the levels (collisional excitation, de-excitation, ionization, recombination, photoionization, bound–bound processes). For the analysis of Type Ia SNe and core collapse SNe (Types Ib, Ic and II) Fe group elements are particularly important. Unfortunately little data is currently available and most noticeably absent are the photoionization cross-sections for the Fe-peaks which have high abundances in SNe. Important interactions for both photoionization and electron-impact excitation are calculated using the relativistic Dirac atomic R-matrix codes (DARC) for low-ionization stages of Cobalt. All results are calculated up to photon energies of 45 eV and electron energies up to 20 eV. The wavefunction representation of Co III has been generated using GRASP0 by including the dominant 3d⁷, 3d⁶[4s, 4p], 3p⁴3d⁹ and 3p⁶3d⁹ configurations, resulting in 292 fine structure levels. Electron-impact collision strengths and Maxwellian averaged effective collision strengths across a wide range of astrophysically relevant temperatures are computed for Co III. In addition, statistically weighted level-resolved ground and metastable photoionization cross-sections are presented for Co II and compared directly with existing work.

A 'before and after' study of nursing students' self-assessed competence in identifying the needs of older patients in hospital using an educational workbook.

Background: A core component of nurse education is clinical practice in order to support the development of clinical skills and competence. Assessment and measurement of the clinical competence of nursing students is important to gauge their professional development and educational needs.

Aim: To evaluate the impact of an Older Persons’ Assessment Educational Workbook (OPAEW) and explore second year nursing students’ competence and their opinions and use of the workbook.

Methods: A ‘before and after’ pre-experimental design was undertaken with n=6 second year nursing students. Outcome measures were the Nursing Competencies Questionnaire and the Self-efficacy in Clinical Performance Scale. Content analysis of workbooks and a survey (n=5) of opinions regarding the workbook was undertaken.

Findings: Pre and post test results for the study (n=5) were tested to determine if there was a relationship between changes in the NCQ and SECP repeated measures and use of an OPAEW. Testing identified evidence of a statistically significant difference for both SECP measures (SECP28 p=0.043; SECP7 p=0.042), with no clear statistical evidence of a difference for the NCQ (p=0.08). A weak negative association (NCQ ρ=-0.600 p=0.285; SECP28 ρ=-0.300 p=0.624; SECP7 ρ=-0.205 p=0.741), was found indicating that those participants who scored the lowest scores at the start of the study, benefited most from the workbook.

Content analysis of the OPAEW (n=5) found that 3 of the 5 participants completed all components of the workbook, with a mean of 1051 words used (SD 281.8). Through the survey (n=5) students reported the workbook as a useful guide when undertaking a patient assessment.

Conclusions: The OPAEW showed potential as an intervention to support the development of nursing students’ competence in older person assessment skills.

A 'before and after' study of nursing students' self-assessed competence in identifying the needs of older patients in hospital using an educational workbook.

Background: A core component of nurse education is clinical practice in order to support the development of clinical skills and competence. Assessment and measurement of the clinical competence of nursing students is important to gauge their professional development and educational needs.

Aim: To evaluate the impact of an Older Persons’ Assessment Educational Workbook (OPAEW) and explore second year nursing students’ competence and their opinions and use of the workbook.

Methods: A ‘before and after’ pre-experimental design was undertaken with n=6 second year nursing students. Outcome measures were the Nursing Competencies Questionnaire and the Self-efficacy in Clinical Performance Scale. Content analysis of workbooks and a survey (n=5) of opinions regarding the workbook was undertaken.

Findings: Pre and post test results for the study (n=5) were tested to determine if there was a relationship between changes in the NCQ and SECP repeated measures and use of an OPAEW. Testing identified evidence of a statistically significant difference for both SECP measures (SECP28 p=0.043; SECP7 p=0.042), with no clear statistical evidence of a difference for the NCQ (p=0.08). A weak negative association (NCQ ρ=-0.600 p=0.285; SECP28 ρ=-0.300 p=0.624; SECP7 ρ=-0.205 p=0.741), was found indicating that those participants who scored the lowest scores at the start of the study, benefited most from the workbook.

Content analysis of the OPAEW (n=5) found that 3 of the 5 participants completed all components of the workbook, with a mean of 1051 words used (SD 281.8). Through the survey (n=5) students reported the workbook as a useful guide when undertaking a patient assessment.

Conclusions: The OPAEW showed potential as an intervention to support the development of nursing students’ competence in older person assessment skills.

Testing the psychometric properties of two self-report clinical competence scales for nursing students.

Background: It is important to assess the clinical competence of nursing students to gauge their educational needs. Competence can be measured by self-assessment tools; however, Anema and McCoy (2010) contend that currently available measures should be further psychometrically tested.
Aim: To test the psychometric properties of Nursing Competencies Questionnaire (NCQ) and Self-Efficacy in Clinical Performance (SECP) clinical competence scales.
Method: A non-randomly selected sample of n=248 2nd year nursing students completed NCQ, SECP and demographic questionnaires (June and September 2013). Mokken Scaling Analysis (MSA) was used to investigate structural validity and scale properties; convergent and discriminant validity and reliability were also tested for each scale.
Results: MSA analysis identified that the NCQ is a unidimensional scale with strong scale scalability coefficients Hs =0.581; but limited item rankability HT =0.367. The SECP scale MSA suggested that the scale could be potentially split into two unidimensional scales (SECP28 and SECP7), each with good/reasonable scalablity psychometric properties as summed scales but negligible/very limited scale rankability (SECP28: Hs = 0.55, HT=0.211; SECP7: Hs = 0.61, HT=0.049). Analysis of between cohort differences and NCQ/SECP scores produced evidence of discriminant and convergent validity; good internal reliability was also found: NCQ α = 0.93, SECP28 α = 0.96 and SECP7 α=0.89.

Discussion: In line with previous research further evidence of the NCQ’s reliability and validity was demonstrated. However, as the SECP findings are new and the sample small with reference to Straat and colleagues (2014), the SECP results should be interpreted with caution and verified on a second sample.
Conclusions: Measurement of perceived self-competence could start early in a nursing programme to support students’ development of clinical competence. Further testing of the SECP scale with larger nursing student samples from different programme years is indicated.

References:
Anema, M., G and McCoy, JK. (2010) Competency-Based Nursing Education: Guide to Achieving Outstanding Learner Outcomes. New York: Springer.
Straat, JH., van der Ark, LA and Sijtsma, K. (2014) Minimum Sample Size Requirements for Mokken Scale Analysis Educational and Psychological Measurement 74 (5), 809-822.