Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).

FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.

INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Assessment of the impact speed and angle conditions for the EN1317 barrier tests

Roadside safety barriers designs are tested with passenger cars in Europe using standard EN1317 in which the impact angle for normal, high and very high containment level tests is 20°. In comparison to EN1317, the US standard MASH has higher impact angles for cars and pickups (25°) and different vehicle masses. Studies in Europe (RISER) and the US have shown values for the 90th percentile impact angle of 30°–34°. Thus, the limited evidence available suggests that the 20° angle applied in EN 1317 may be too low.
The first goal of this paper is to use the US NCHRP database (Project NCHRP 17–22) to assess the distribution of impact angle and collision speed in recent ROR accidents. Second, based on the findings of the statistical analysis and on analysis of impact angles and speeds in the literature, an LS-DYNA finite element analysis was carried out to evaluate the normal containment level of concrete barriers in non-standard collisions. The FE model was validated against a crash test of a portable concrete barrier carried out at the UK Transport Research Laboratory (TRL).
The accident data analysis for run-off road accidents indicates that a substantial proportion of accidents have an impact angle in excess of 20°. The baseline LS-DYNA model showed good comparison with experimental acceleration severity index (ASI) data and the parametric analysis indicates a very significant influence of impact angle on ASI. Accordingly, a review of European run-off road accidents and the configuration of EN 1317 should be performed.

Making meaningful connections: Using insights from social pedagogy in statutory child and family social work practice

Reports into incidents of child death and serious injury have highlighted consistently concern about the capacity of social workers to communicate skilfully with children. Drawing on data collected as part of an Economic and Social Research Council funded UK-wide research project exploring social workers’ communicative practices with children, this paper explores how approaches informed by social pedagogy can assist social workers in connecting and communicating children. The qualitative research included data generated from 82 observations of social workers’ everyday encounters with children. Social pedagogical concepts of ‘haltung’ (attitude), ‘head, heart and hands’ and ‘the common third’ are outlined as potentially helpful approaches for facilitating the intimacies of inter-personal connections and enhancing social workers’ capacity to establish and sustain meaningful communication and relationships with children in the face of austere social, political and organisational contexts.

How Prepared are UK Medical Graduates for Practice? Final report from a programme of research commissioned by the General Medical Council

This programme of research aimed to understand the extent to which current UK medical graduates are prepared for practice. Commissioned by the General Medical Council, we conducted: (1) A Rapid Review of the literature between 2009 and 2013; (2) narrative interviews with a range of stakeholders; and (3) longitudinal audio-diaries with Foundation Year 1 doctors. The Rapid Review (RR) resulted in data from 81 manuscripts being extracted and mapped against a coding framework (including outcomes from Tomorrow's Doctors (2009) (TD09)). A narrative synthesis of the data was undertaken. Narrative interviews were conducted with 185 participants from 8 stakeholder groups: F1 trainees, newly registered trainee doctors, clinical educators, undergraduate and postgraduate deans and foundation programme directors, other healthcare professionals, employers, policy and government and patient and public representatives. Longitudinal audio-diaries were recorded by 26 F1 trainees over 4 months. The data were analysed thematically and mapped against TD09. Together these data shed light onto how preparedness for practice is conceptualised, measured, how prepared UK medical graduates are for practice, the effectiveness of transition interventions and the currently debated issue of bringing full registration forward to align with medical students’ graduation. Preparedness for practice was conceptualised as both a long- and short-term venture that included personal readiness as well as knowledge, skills and attitudes. It has mainly been researched using self-report measures of generalised incidents that have been shown to be problematic. In terms of transition interventions: assistantships were found to be valuable and efficacious for proactive students as team members, shadowing is effective when undertaken close to employment/setting of F1 post and induction is generally effective but of inconsistent quality. The August transition was highlighted in our interview and audio-diary data where F1s felt unprepared, particularly for the step-change in responsibility, workload, degree of multitasking and understanding where to go for help. Evidence of preparedness for specific tasks, skills and knowledge was contradictory: trainees are well prepared for some practical procedures but not others, reasonably well prepared for history taking and full physical examinations, but mostly unprepared for adopting an holistic understanding of the patient, involving patients in their care, safe and legal prescribing, diagnosing and managing complex clinical conditions and providing immediate care in medical emergencies. Evidence for preparedness for interactional and interpersonal aspects of practice was inconsistent with some studies in the RR suggesting graduates were prepared for team working and communicating with colleagues and patients, but other studies contradicting this. Interview and audio-diary data highlights concerns around F1s preparedness for communicating with angry or upset patients and relatives, breaking bad news, communicating with the wider team (including interprofessionally) and handover communication. There was some evidence in the RR to suggest that graduates were unprepared for dealing with error and safety incidents and lack an understanding of how the clinical environment works. Interview and audio-diary data backs this up, adding that F1s are also unprepared for understanding financial aspects of healthcare. In terms of being personally prepared, RR, interview and audio diary evidence is mixed around graduates’ preparedness for identifying their own limitations, but all data points to graduates’ difficulties in the domain of time management. In terms of personal and situational demographic factors, the RR found that gender did not typically predict perceptions of preparedness, but graduates from more recent cohorts, graduate entry students, graduates from problem based learning courses, UK educated graduates and graduates with an integrated degree reported feeling better prepared. The longitudinal audio-diaries provided insights into the preparedness journey for F1s. There seems to be a general development in the direction of trainees feeling more confident and competent as they gain more experience. However, these developments were not necessarily linear as challenging circumstances (e.g. new specialty, new colleagues, lack of staffing) sometimes made them feel unprepared for situations where they had previously indicated preparedness.

The Changing Context for Planning Education in the UK and the Prospects for Research-Led, Practice-Engaged Teaching

The UK’s Royal Town Planning Institute (RTPI) celebrates its centenary in 2014, marking 100 years of close relationships between university-based Planning Schools and a professional body focussed on planning practice. During this period, the context for university education and the very idea of planning has changed dramatically contributing to a continual renegotiation of the relationships between the planning profession and the educational institutions it accredits. These changes have been particularly acute in the last ten years where a number of factors have forced a rapid change in the nature of planning education in the UK. This has included a boom and then slump in the number of planning students linked to the national economic situation, a reorganisation of many planning schools and their merger with cognate disciplines such as geography and an increased focus of research output, rather than professional engagement the key institutional indicator of success. This last factor adds a particularly new dimension to the profession-university relationship, which could potentially lead to either a straining of tensions or a synergy through research-led teaching that could significantly benefit both.

This paper will briefly review the evolution of UK planning schools and the co-evolution of the main ideas informing planning education. It will then describe the current profile of UK planning schools, based on an extensive national survey conducted on behalf of the Royal Town Planning Institute. The paper will then critically review the main challenges and opportunities facing UK Planning Schools in the context of changes in both planning practice and higher education. It will then move on to the concept of research-led teaching, drawing on current practice in the UK and review how well this concept serves students and the idea of developing reflective planning practitioners. Finally, the paper will seek to draw broad lessons from the experience of the UK and reflect on the type of planning education that can best serve planning professions in a variety of international contexts in the future.

The Changing Context for Planning Education in the UK and the Prospects for Research-Led, Practice-Engaged Teaching

The UK’s Royal Town Planning Institute (RTPI) has celebrated its centenary in 2014, marking 100 years of close relationships between university-based planning schools and a professional body focused on planning practice. During this period, the context for university education and the very idea of planning have changed dramatically contributing to a continual renegotiation of the relationships between the planning profession and the educational institutions it accredits. These changes have been particularly pronounced in the last 10 years where a number of factors have forced a rapid change in the nature of planjavascript:void(0);ning education in the UK. This has included a boom and then slump in the number of planning students linked to the dynamics of national economic situation, a reorganization of many planning school curricula, and their merger with cognate disciplines such as geography and an increased focus on research output, rather than professional engagement as the key indicator of institutional success. This last factor adds a particularly new dimension to the profession-university relationship, which could potentially lead to either straining of tensions or a synergy through research-led teaching that could significantly benefit both. This chapter will briefly review the evolution of UK planning schools and of the main ideas informing planning education. It will then describe the current profile of UK planning schools, based on an extensive national survey conducted on behalf of the Royal Town Planning Institute. The paper will then critically review the main challenges and opportunities facing UK planning schools in the context of changes in both planning practice and higher education. It will then move on to the concept of research-led teaching, drawing on current practice in the UK and review how well this concept serves students and the idea of developing reflective planning practitioners. Finally, the paper will seek to draw broad lessons from the experience of the UK and reflect on the type of planning education that can best serve planning professions in a variety of international contexts in the future.

A national survey of the mangement of delirium in UK intensive care units

Background: Delirium is an acute organ dysfunction common amongst patients treated in intensive care units. The associated morbidity and mortality are known to be substantial. Previous surveys have described which screening tools are used to diagnose delirium and which medications are used to treat delirium, but these data are not available for the United Kingdom. Aim: This survey aimed to describe the UK management of delirium by consultant intensivists. Additionally, knowledge and attitudes towards management of delirium were sought. The results will inform future research in this area. Methods: A national postal survey of members of the UK Intensive Care Society was performed. A concise two page questionnaire survey was sent, with a second round of surveys sent to non-respondents after 6 weeks. The questionnaire was in tick-box format. Results: Six hundred and eighty-one replies were received from 1308 questionnaires sent, giving a response rate of 52%. Twenty-five percent of respondents routinely screen for delirium, but of these only 55% use a screening tool validated for use in intensive care. The majority (80%) of those using a validated instrument used the Confusion Assessment Method for the Intensive Care Unit. Hyperactive delirium is treated pharmacologically by 95%; hypoactive delirium is treated pharmacologically by 25%, with haloperidol the most common agent used in both. Over 80% of respondents agreed that delirium prolongs mechanical ventilation and hospital stay and requires active treatment. Conclusions: This UK survey demonstrates screening for delirium is sporadic. Pharmacological treatment is usually with haloperidol in spite of the limited evidence to support this practice. Hypoactive delirium is infrequently treated pharmacologically.

Cystic fibrosis research in allied health and nursing professions

This report is the result of the "Allied Health and Nursing Professions Working Group" meeting which took place in Verona, Italy, November 2009, which was organised by the European Cystic Fibrosis Society, and involved 32 experts. The meeting was designed to provide a "roadmap" of high priority research questions that can be addressed by Allied Health Professionals (AHP) and nursing. The other goal was to identify research skills that would be beneficial to AHP and nursing researchers and would ultimately improve the research capacity and capability of these professions. The following tasks were accomplished: 1) a Delphi survey was used to identify high priority research areas and themes, 2) common research designs used in AHP and nursing research were evaluated in terms of their strengths and weaknesses, 3) methods for assessing the clinimetric and psychometric properties, as well as feasibility, of relevant outcome measures were reviewed, and 4) a common skill set for AHPs and nurses undertaking clinical research was agreed on and will guide the planning of future research opportunities. This report has identified important areas and themes for future research which include: adherence; physical activity/exercise; nutritional interventions; interventions for the newborn with CF and evaluation of outcome measures for use in AHP and nursing research. It has highlighted the significant challenges AHPs and nurses experience in conducting clinical research, and proposes strategies to overcome these challenges. It is hoped that this report will encourage research initiatives that assess the efficacy/effectiveness of AHP and nursing interventions in order to improve the evidence base. This should increase the quality of research conducted by these professions, justify services they currently provide, and expand their skills in new areas, with the ultimate goal of improving care for patients with CF.

Stress, Positive Psychology and the National Student Survey

The aim was to explore the predictive ability of sources of stress and a range of dispositional and coping behaviours on student satisfaction and motivation. Most research exploring sources of stress and coping in students construes stress as psychological distress, with little attempt to consider positive experiences of stress. A questionnaire was administered to 120 first-year UK psychology students. Questions were asked which measured sources of stress when rated as likely to contribute to distress (a hassle) and likely to help one achieve (an uplift). The sources of stress were amended from the UK National Student Survey (NSS, 2011). Support, control, self-efficacy, personality and coping style were also measured, along with their potential affect on
course satisfaction, motivation and feeling part of a learning community. The sources of stress likely to lead to distress were more often significant than sources of stress likely to lead to positive, eustress states. Ironically,
factors one would consider would help students, such as the university support facilities, only did so when rated as a hassle, not as an uplift. Published university league tables draw heavily on student course satisfaction but this negatively correlated with intellectual motivation and feeling part of a learning
community. This suggests course satisfaction alone reveals an incomplete picture of the student experience. Course educators need to consider how course experiences contribute not just to potential distress but to
potential eustress. Teaching quality, effective support and work-life balance are key to student satisfaction and motivation. How educators interact with their students and the opportunities they create in and outside the class to promote peer support are likely to enhance satisfaction and motivation.