Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

BACKGROUND:
Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE--an international, open-label, randomised controlled trial--uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the preplanned, second intermediate analysis comparing hormone therapy plus celecoxib (arm D) with hormone therapy alone (control arm A).
METHODS:
Eligible patients were men with newly diagnosed or rapidly relapsing prostate cancer who were starting long-term hormone therapy for the first time. Hormone therapy was given as standard care in all trial arms, with local radiotherapy encouraged for newly diagnosed patients without distant metastasis. Randomisation was done using minimisation with a random element across seven stratification factors. Patients randomly allocated to arm D received celecoxib 400 mg twice daily, given orally, until 1 year or disease progression (including prostate-specific antigen [PSA] failure). The intermediate outcome was failure-free survival (FFS) in three activity stages; the primary outcome was overall survival in a subsequent efficacy stage. Research arms were compared pairwise against the control arm on an intention-to-treat basis. Accrual of further patients was discontinued in any research arm showing safety concerns or insufficient evidence of activity (lack of benefit) compared with the control arm. The minimum targeted activity at the second intermediate activity stage was a hazard ratio (HR) of 0·92. This trial is registered with ClinicalTrials.gov, number NCT00268476, and with Current Controlled Trials, number ISRCTN78818544.
FINDINGS:
2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly allocated to receive hormone therapy alone (control group; arm A) and 291 to receive hormone therapy plus celecoxib (arm D). At the preplanned analysis of the second intermediate activity stage, with 305 FFS events (209 in arm A, 96 in arm D), there was no evidence of an advantage for hormone therapy plus celecoxib over hormone therapy alone: HR 0·94 (95% CI 0·74-1·20). [corrected]. 2-year FFS was 51% (95% CI 46-56) in arm A and 51% (95% CI 43-58) in arm D. There was no evidence of differences in the incidence of adverse events between groups (events of grade 3 or higher were noted at any time in 123 [23%, 95% CI 20-27] patients in arm A and 64 [25%, 19-30] in arm D). The most common grade 3-5 events adverse effects in both groups were endocrine disorders (55 [11%] of patients in arm A vs 19 [7%] in arm D) and musculoskeletal disorders (30 [6%] of patients in arm A vs 15 [6%] in arm D). The independent data monitoring committee recommended stopping accrual to both celecoxib-containing arms on grounds of lack of benefit and discontinuing celecoxib for patients currently on treatment, which was endorsed by the trial steering committee.
INTERPRETATION:
Celecoxib 400 mg twice daily for up to 1 year is insufficiently active in patients starting hormone therapy for high-risk prostate cancer, and we do not recommend its use in this setting. Accrual continues seamlessly to the other research arms and follow-up of all arms will continue to assess effects on overall survival.

A parenting intervenion for childhood behavioral problems: a randomised controlled trial in disadvantaged Community-based settings:A randomized controlled trial in disadvantaged community-based settings

Objective: A community-based randomized controlled trial (RCT) was conducted in urban areas characterized by high levels of disadvantage to test the effectiveness of the Incredible Years BASIC parent training program (IYBP) for children with behavioral problems. Potential moderators of intervention effects on child behavioral outcomes were also explored. Method: Families were included if the child (aged 32-88 months) scored above a clinical cutoff on the Eyberg Child Behavior Inventory (ECBI). Participants (n = 149) were randomly allocated on a 2:1 ratio to an intervention group (n = 103) or a waiting-list control group (n = 46). Child behavior, parenting skills, and parent well-being were assessed at baseline and 6 months later using parent-report and independent observations. An intention-to-treat analysis of covariance was used to examine postintervention differences between groups. Results: Statistically significant differences in child disordered behavior favored the intervention group on the ECBI Intensity (effect size = 0.7, p

Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils:a randomized, placebo-controlled clinical trial

Increased numbers of neutrophils are reported in the airways of patients with severe asthma. It is not clear if they contribute to the lack of control and severity. There are currently no strategies to investigate this by decreasing neutrophil numbers in the airways.

Evidence from a Baseline Study of Teachers and Young People in Northern Ireland: Implications for Peace Education.

Peace education initiatives in schools are often based on social psychological theories assuming that social identity affects ingroup and outgroup attitudes and, in turn, behaviors relating to relevant outgroups. However, research evidence on the role of young people’s social identity has often failed to take account of different social identity dimensions or to conceptualise outgroup behavior in the context of young people’s understandings of the social world. While recent research relating to bullying and bystander behavior amongst young people has addressed the latter point, this has rarely been considered in conjunction with a differentiated view of social identity. This paper is therefore distinctive as it will address the role of social identity dimensions with regards to behavior as captured in bystander scenarios relating to intergroup discrimination. This is particularly important in the context of divided societies, where peace education initiatives are crucial in promoting positive community relations for the future and where such initiative may be hampered by communities’ concerns about loss of identity and hardened intergroup attitudes. Furthermore, previous research frequently highlighted teachers’ fears to tackle outgroup attitudes in the classroom, especially in contexts where pupils and the wider school community are seen as entrenched in community divisions (Hughes, Donnelly, Hewstone, Gallagher & Carlisle, 2010). However, there is no research investigating the relationship between pupils’ attitudes and teacher confidence to talk about such issues in the classroom, which is explored in this paper.

In the context of Northern Ireland, a divided society emerging from sectarian conflict, social identity, outgroup attitudes and outgroup behaviours have been key concepts addressed by peace educators for many years. Building on this work, this paper provides a detailed picture of young people’s strength of group identification and their willingness to explore ingroup perspectives, sectarian attitudes and their reported willingness to challenge sectarian bullying. Using data from a baseline survey, which forms part of a randomized control trial investigating the effect of an educational intervention aimed to promote reconciliation, the sample involved young people of different denominational backgrounds, attending separate school sectors. The baseline data will be used to compare with post intervention data. Therefore, the data and its findings would be of particular interest to educators and policy makers in other European countries who are working to develop peace education interventions in societies emerging from conflict. Additionally, this paper considers the results from a baseline teacher survey, collected before training and teaching of the intervention began. The teacher survey focused on confidence in tackling sectarian issues in the classroom, previous experience of teaching such issues and their hopes and concerns for the reconciliation intervention.

This paper therefore set out to investigate the relationship between dimensional concept of social identity, sectarian attitudes and pupils’ reported willingness to challenge sectarian bullying and to compare this with their teachers’ attitudes to teaching about sectarian issues in the classroom.



Method

The pupil sample included 35 primary and post-primary schools and about 800 pupils from 8-11 years old who completed an online questionnaire in December 2011 and January 2012. Main instruments for young people’s survey included an adapted version of the Multi-ethnic identity measure (Phinney, 1992) incorporating the dimensions identity affirmation and exploration, outgroup attitude scales, including an adaptation of the social distance measure (Bogardus, 1947), as well as a measure adapted from Palmer and Cameron (2011) involving scenarios to capture pupils’ intentions in bystander situations relating to intergroup discrimination. Results are analysed using regression analysis and take account of potential gender and religious differences. The teacher questionnaire was completed by the 35 primary and post-primary teachers who will deliver the intervention. Results are analysed in terms of how teachers’ responses compare with their pupil attitudes by considering their confidence in tackling sectarian issues in the classroom and how their previous experience and training relate to their hopes and concerns for the intervention.


Expected Outcomes

Results from the young people’s survey are discussed in the light of the role of social identity dimensions and their relationship to sectarian attitudes and reported bystander behaviour in sectarian school incidents. Furthermore, results related to pupils’ sectarian attitudes will be compared with teachers’ reported confidence in tackling sectarianism in the classroom. The teacher questionnaire also presents interesting findings in relation to teachers’ previous training and experience and how this may influence different perspectives on peace and reconciliation interventions and their expectations of what these could achieve. The paper concludes with potential implications for peace education initiatives and related teacher training in Northern Ireland and beyond. The implications will be of particular interest to policy makers, educators and those working in the area of peace education to design and implement interventions.


References

Bogardus, E. S. (1947) Measurement of Personal-Group Relations. Sociometry, 10: 4: 306–311. Hughes, J., Donnelly, C., Hewstone, M., Gallagher, T. & Carlisle, K. (2010) School partnerships and reconciliation: An evaluation of school collaboration in Northern Ireland. Belfast: Queen’s University Belfast. Available online: http://www.schoolsworkingtogether.com/documents/School%20collaboration%20in%20NI%202010.pdf. (accessed 27th Jan 2010) Palmer, S. & Cameron, L. (2011, May). What are the moderators and mediators of children’s bystander behaviour in the context of intergroup discrimination? Paper session presented at the UNA Global Biennial Conference 2011: Building Peaceable Communities: The Power of Early Childhood, Amsterdam, Holland. Phinney, J. S. (1992). The Multigroup Ethnic Identity Measure: A new scale for use with diverse groups. Journal of Adolescent Research, 7, 156–176.

Steroid injection for inferior heel pain: a randomised controlled trial

BACKGROUND:

Plantar fasciitis is a common cause of heel pain. The aim of this study was twofold: to compare steroid injection with placebo injection and to compare ultrasound guided with unguided steroid injection in the management of this condition.

METHODS:

65 patients with inferior heel pain were recruited between November 2008 and June 2011. Heel pain was measured using a visual analogue scale (VAS) at baseline and follow-up 6 and 12 weeks after injection.

RESULTS:

22 patients were randomised to ultrasound guided steroid injection, 21 patients to palpation guided steroid injection and 22 to ultrasound guided placebo injection. There was a significant difference in VAS scores between the groups at 6 and 12 weeks (p=0.018 and p=0.004, respectively). There was a 19.7 (95% CI 2.5 to 37.0) difference in mean VAS scores at 6 weeks between the ultrasound guided steroid group and the placebo group and a 24.0 (95% CI 6.6 to 41.3) difference between the unguided steroid group and the placebo group at 6 weeks. At 12 weeks, the mean difference was 25.1 (95% CI 6.5 to 43.6) and 28.4 (95% CI 11.1 to 45.7) respectively between both steroid injection groups and the placebo group. There was no difference in VAS scores following steroid injection between the ultrasound guided and the unguided groups at either time point. Plantar fascia thickness was significantly reduced after injection in both active treatment groups (p=0.00).

CONCLUSIONS:

In this study, steroid injection showed a clear benefit over placebo at 6 weeks and this difference was maintained at 12 weeks.Trial Registration No ISRCTN79628180 (www.controlled-trials.com).

A prospective randomised trial of a "test and treat" policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic

Management of dyspepsia remains a controversial area. Although the European Helicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do not exhibit alarm symptoms, this strategy has not been subjected to clinical trial.

Maintenance therapy with cisapride after healing of erosive oesophagitis:a double-blind placebo-controlled trial

There are few data on the role of prokinetic agents as maintenance therapy in moderately severe reflux oesophagitis despite the high relapse rate of this condition after healing.